Vaccines

16 pages, 746 KiB

Open AccessEditor’s ChoiceReview

COVID-19 Vaccine Booster Strategies for Omicron SARS-CoV-2 Variant: Effectiveness and Future Prospects

by Dorota Zarębska-Michaluk, Chenlin Hu, Michał Brzdęk, Robert Flisiak and Piotr Rzymski

Vaccines 2022, 10(8), 1223; https://doi.org/10.3390/vaccines10081223 - 30 Jul 2022

Cited by 16 | Viewed by 18063

In the light of the lack of authorized COVID-19 vaccines adapted to the Omicron variant lineage, the administration of the first and second booster dose is recommended. It remains important to monitor the efficacy of such an approach in order to inform future [...] Read more.

In the light of the lack of authorized COVID-19 vaccines adapted to the Omicron variant lineage, the administration of the first and second booster dose is recommended. It remains important to monitor the efficacy of such an approach in order to inform future preventive strategies. The present paper summarizes the research progress on the effectiveness of the first and second booster doses of COVID-19. It also discusses the potential approach in vaccination strategies that could be undertaken to maintain high levels of protection during the waves of SARS-CoV-2 infections. Although this approach can be based, with some shortcomings, on the first-generation vaccines, other vaccination strategies should be explored, including developing multiple antigen-based (multivariant-adapted) booster doses with enhanced durability of immune protection, e.g., through optimization of the half-life of generated antibodies. Full article

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10 pages, 1092 KiB

Open AccessEditor’s ChoiceArticle

Correlation between Adverse Events and Antibody Titers among Healthcare Workers Vaccinated with BNT162b2 mRNA COVID-19 Vaccine

by Itzchak Levy, Einav Gal Levin, Liraz Olmer, Gili Regev-Yochay, Nancy Agmon-Levin, Anat Wieder-Finesod, Victoria Indenbaum, Karin Herzog, Ram Doolman, Keren Asraf, Rebecca Halperin, Yaniv Lustig and Galia Rahav

Vaccines 2022, 10(8), 1220; https://doi.org/10.3390/vaccines10081220 - 30 Jul 2022

Cited by 17 | Viewed by 2754

Abstract

Objectives: The BNT162b2 mRNA COVID-19 vaccine has been found to be highly effective in preventing COVID-19 but is associated with increased reactogenicity. We aimed to examine the correlation between immunogenicity and reactogenicity of the BNT162b2 vaccine. Methods: Subjects without prior SARS-CoV-2 infection that [...] Read more.

Objectives: The BNT162b2 mRNA COVID-19 vaccine has been found to be highly effective in preventing COVID-19 but is associated with increased reactogenicity. We aimed to examine the correlation between immunogenicity and reactogenicity of the BNT162b2 vaccine. Methods: Subjects without prior SARS-CoV-2 infection that participated in active surveillance after being vaccinated with the BNT162b2 vaccine were included. Study participants reported adverse drug reactions (ADRs) through questionnaires administered by text message after receiving each dose of the vaccine. A reactogenicity score was developed based on the type and duration of ADRs. In addition, anti-receptor binding domain (RBD) levels and neutralization assays were performed 7–21 and 7–38 days after the first and second vaccine doses, respectively. Associations between ADRs and antibody levels were assessed by Spearman correlations. Multivariable logistic regression analyses were used to identify factors associated with ADRs. Results: A total of 831 health care workers were included. The mean age was 46.5 years (SD = 11.8) and 75.5% were females. 83.4% and 83.3% had at least one local ADR after the first and second doses, respectively. 33% and 83.2% had at least one systemic ADR after the first and second doses, respectively. Multivariate logistic regression analysis found a significant correlation between ADR score and anti-RBD-IgG titers (r = 0.366; p < 0.0001) after adjustment for age, gender, and days after the second vaccination. High anti-RBD-IgG levels, being younger than 55 and being female, were all correlated with increased rates of ADRs. Conclusion: BNT162b2 mRNA COVID-19 vaccine reactogenicity appears to be correlated with higher post-vaccination antibody levels and is independently associated with younger age and female gender. Full article

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17 pages, 1850 KiB

Open AccessEditor’s ChoiceReview

Safety and Efficacy of Influenza Vaccination in Patients Receiving Immune Checkpoint Inhibitors. Systematic Review with Meta-Analysis

by Maria A. Lopez-Olivo, Valeria Valerio, Aliza R. Karpes Matusevich, Marianela Brizio, Michelle Kwok, Yimin Geng, Maria E. Suarez-Almazor and Ines Colmegna

Vaccines 2022, 10(8), 1195; https://doi.org/10.3390/vaccines10081195 - 27 Jul 2022

Cited by 14 | Viewed by 2622

Abstract

The potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. [...] Read more.

The potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. We searched five electronic databases until 01/2022. Two authors independently selected studies, appraised their quality, and collected data. The primary outcome was the determination of pooled irAE rates. Secondary outcomes included determination of immunogenicity and influenza infection rates and cancer-related outcomes. Nineteen studies (26 publications, n = 4705) were included; 89.5% were observational. Vaccinated patients reported slighter lower rates of irAEs compared to unvaccinated patients (32% versus 41%, respectively). Seroprotection for influenza type A was 78%–79%, and for type B was 75%. Influenza and irAE-related death rates were similar between groups. The pooled proportion of participants reporting a laboratory-confirmed infection was 2% (95% CI 0% to 6%), and influenza-like illness was 14% (95% CI 2% to 32%). No differences were reported on the rates of laboratory-confirmed infection between vaccinated and unvaccinated patients. Longer progression-free and overall survival was also observed in vaccinated compared with unvaccinated patients. Current evidence suggests that influenza vaccination is safe in patients receiving ICIs, does not increase the risk of irAEs, and may improve survival. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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27 pages, 1796 KiB

Open AccessEditor’s ChoiceReview

Nanoparticle- and Microparticle-Based Vaccines against Orbiviruses of Veterinary Importance

by Luis Jiménez-Cabello, Sergio Utrilla-Trigo, Natalia Barreiro-Piñeiro, Tomás Pose-Boirazian, José Martínez-Costas, Alejandro Marín-López and Javier Ortego

Vaccines 2022, 10(7), 1124; https://doi.org/10.3390/vaccines10071124 - 14 Jul 2022

Cited by 8 | Viewed by 3961

Abstract

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are widespread arboviruses that cause important economic losses in the livestock and equine industries, respectively. In addition to these, another arthropod-transmitted orbivirus known as epizootic hemorrhagic disease virus (EHDV) entails a major threat as [...] Read more.

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are widespread arboviruses that cause important economic losses in the livestock and equine industries, respectively. In addition to these, another arthropod-transmitted orbivirus known as epizootic hemorrhagic disease virus (EHDV) entails a major threat as there is a conducive landscape that nurtures its emergence in non-endemic countries. To date, only vaccinations with live attenuated or inactivated vaccines permit the control of these three viral diseases, although important drawbacks, e.g., low safety profile and effectiveness, and lack of DIVA (differentiation of infected from vaccinated animals) properties, constrain their usage as prophylactic measures. Moreover, a substantial number of serotypes of BTV, AHSV and EHDV have been described, with poor induction of cross-protective immune responses among serotypes. In the context of next-generation vaccine development, antigen delivery systems based on nano- or microparticles have gathered significant attention during the last few decades. A diversity of technologies, such as virus-like particles or self-assembled protein complexes, have been implemented for vaccine design against these viruses. In this work, we offer a comprehensive review of the nano- and microparticulated vaccine candidates against these three relevant orbiviruses. Additionally, we also review an innovative technology for antigen delivery based on the avian reovirus nonstructural protein muNS and we explore the prospective functionality of the nonstructural protein NS1 nanotubules as a BTV-based delivery platform. Full article

(This article belongs to the Special Issue Microparticle-Based Vaccines)

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18 pages, 1381 KiB

Open AccessEditor’s ChoiceReview

Pseudomonas aeruginosa: Recent Advances in Vaccine Development

by Matthew Killough, Aoife Maria Rodgers and Rebecca Jo Ingram

Vaccines 2022, 10(7), 1100; https://doi.org/10.3390/vaccines10071100 - 8 Jul 2022

Cited by 43 | Viewed by 13497

Abstract

Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound [...] Read more.

Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound infections, ventilator-associated pneumonia, and chronic infections in people with cystic fibrosis. Antibiotic resistance has rendered many of these infections challenging to treat and novel therapeutic strategies are limited. Multiple clinical studies using well-characterised virulence factors as vaccine antigens over the last 50 years have fallen short, resulting in no effective vaccination being available for clinical use. Nonetheless, progress has been made in preclinical research, namely, in the realms of antigen discovery, adjuvant use, and novel delivery systems. Herein, we briefly review the scope of P. aeruginosa clinical infections and its major important virulence factors. Full article

(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)

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16 pages, 1433 KiB

Open AccessEditor’s ChoiceArticle

Correlates of Zero-Dose Vaccination Status among Children Aged 12–59 Months in Sub-Saharan Africa: A Multilevel Analysis of Individual and Contextual Factors

by Chamberline E. Ozigbu, Bankole Olatosi, Zhenlong Li, James W. Hardin and Nicole L. Hair

Vaccines 2022, 10(7), 1052; https://doi.org/10.3390/vaccines10071052 - 30 Jun 2022

Cited by 15 | Viewed by 3832

Abstract

Despite ongoing efforts to improve childhood vaccination coverage, including in hard-to-reach and hard-to-vaccinate communities, many children in sub-Saharan Africa (SSA) remain unvaccinated. Considering recent goals set by the Immunization Agenda 2030 (IA2030), including reducing the number of zero-dose children by half, research that [...] Read more.

Despite ongoing efforts to improve childhood vaccination coverage, including in hard-to-reach and hard-to-vaccinate communities, many children in sub-Saharan Africa (SSA) remain unvaccinated. Considering recent goals set by the Immunization Agenda 2030 (IA2030), including reducing the number of zero-dose children by half, research that goes beyond coverage to identify populations and groups at greater risk of being unvaccinated is urgently needed. This is a pooled cross-sectional study of individual- and country-level data obtained from Demographic and Health Surveys Program and two open data repositories. The sample includes 43,131 children aged 12–59 months sampled between 2010 and 2020 in 33 SSA countries. Associations of zero-dose status with individual and contextual factors were assessed using multilevel logistic regression. 16.5% of children had not received any vaccines. Individual level factors associated lower odds of zero-dose status included mother’s primary school or high school education, employment, use of antenatal care services and household wealth. Compared to children in countries with lower GDP, children in countries with relatively high GDP had nearly four times greater odds of being unvaccinated. Both individual and contextual factors are correlated with zero-dose status in SSA. Our results can inform efforts to identify and reach children who have not received any vaccines. Full article

(This article belongs to the Special Issue Immunization of Children and Women against Infectious Diseases)

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15 pages, 2305 KiB

Open AccessEditor’s ChoiceArticle

A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease

by Wenjun Zhu, Guodong Liu, Wenguang Cao, Shihua He, Anders Leung, Ute Ströher, Michael J. Fairchild, Rick Nichols, Joseph Crowell, Joan Fusco and Logan Banadyga

Vaccines 2022, 10(7), 1004; https://doi.org/10.3390/vaccines10071004 - 23 Jun 2022

Cited by 12 | Viewed by 3050

Abstract

Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the Filoviridae family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV [...] Read more.

Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the Filoviridae family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Our results demonstrated that a single dose (2 × 10⁶ PFU) of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Moreover, protection was robust, with as little as 200 PFU of vaccine conferring significant protection. Not only does this study highlight the potential predictive value of the guinea pig model in the evaluation of MARV countermeasures, but it also demonstrates consistent and reproducible protection afforded by a clonal vaccine candidate. Indeed, this study identifies PHV01 as a suitable vaccine candidate for advanced development. Full article

(This article belongs to the Special Issue Vaccine Development Needs for Marburg Virus and Sudan Ebolavirus: Leveraging Lessons Learned from the Zaire Ebolavirus)

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19 pages, 373 KiB

Open AccessEditor’s ChoiceReview

Vaccine Preventable Zoonotic Diseases: Challenges and Opportunities for Public Health Progress

by Ann Carpenter, Michelle A. Waltenburg, Aron Hall, James Kile, Marie Killerby, Barbara Knust, Maria Negron, Megin Nichols, Ryan M. Wallace, Casey Barton Behravesh, Jennifer H. McQuiston and the Vaccine Preventable Zoonotic Disease Working Group

Vaccines 2022, 10(7), 993; https://doi.org/10.3390/vaccines10070993 - 22 Jun 2022

Cited by 20 | Viewed by 7589

Abstract

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and [...] Read more.

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and implement vaccine interventions to reduce zoonotic disease impacts are often limited to the veterinary and agricultural sectors and do not reflect the shared burden of disease. Multisectoral collaboration, including co-development opportunities for human and animal vaccines, expanding vaccine use to include animal reservoirs such as wildlife, and strategically using vaccines to interrupt complex transmission cycles is needed. Addressing zoonoses requires a multi-faceted One Health approach, wherein vaccinating people and animals plays a critical role. Full article

(This article belongs to the Special Issue Veterinary Vaccines and One Health)

15 pages, 1010 KiB

Open AccessEditor’s ChoiceArticle

Predictors of Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab

by Victoria Furer, Tali Eviatar, Devy Zisman, Hagit Peleg, Yolanda Braun-Moscovici, Alexandra Balbir-Gurman, Daphna Paran, David Levartovsky, Michael Zisapel, Ofir Elalouf, Ilana Kaufman, Adi Broyde, Ari Polachek, Joy Feld, Amir Haddad, Tal Gazitt, Muna Elias, Nizar Higazi, Fadi Kharouf, Sara Pel, Sharon Nevo and Ori Elkayam Show full author list Hide full author list

Vaccines 2022, 10(6), 901; https://doi.org/10.3390/vaccines10060901 - 6 Jun 2022

Cited by 20 | Viewed by 3019

Abstract

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 [...] Read more.

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1–10) vs. 5 (1–15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046–0.96, p = 0.044 and OR 0.189, 95% CI 0.036–0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients. Full article

(This article belongs to the Topic Global Analysis of SARS-CoV-2 Serology)

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26 pages, 748 KiB

Open AccessEditor’s ChoiceReview

An Overview of Vaccine Adjuvants: Current Evidence and Future Perspectives

by Alessio Facciolà, Giuseppa Visalli, Antonio Laganà and Angela Di Pietro

Vaccines 2022, 10(5), 819; https://doi.org/10.3390/vaccines10050819 - 22 May 2022

Cited by 123 | Viewed by 23619

Abstract

Vaccinations are one of the most important preventive tools against infectious diseases. Over time, many different types of vaccines have been developed concerning the antigen component. Adjuvants are essential elements that increase the efficacy of vaccination practises through many different actions, especially acting [...] Read more.

Vaccinations are one of the most important preventive tools against infectious diseases. Over time, many different types of vaccines have been developed concerning the antigen component. Adjuvants are essential elements that increase the efficacy of vaccination practises through many different actions, especially acting as carriers, depots, and stimulators of immune responses. For many years, few adjuvants have been included in vaccines, with aluminium salts being the most commonly used adjuvant. However, recent research has focused its attention on many different new compounds with effective adjuvant properties and improved safety. Modern technologies such as nanotechnologies and molecular biology have forcefully entered the production processes of both antigen and adjuvant components, thereby improving vaccine efficacy. Microparticles, emulsions, and immune stimulators are currently in the spotlight for their huge potential in vaccine production. Although studies have reported some potential side effects of vaccine adjuvants such as the recently recognised ASIA syndrome, the huge worth of vaccines remains unquestionable. Indeed, the recent COVID-19 pandemic has highlighted the importance of vaccines, especially in regard to managing future potential pandemics. In this field, research into adjuvants could play a leading role in the production of increasingly effective vaccines. Full article

(This article belongs to the Special Issue Present and Future Vaccinations: Current Strategies and New Perspectives in the Fight against Infectious Diseases)

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17 pages, 285 KiB

Open AccessEditor’s ChoiceReview

Vaccination for the Prevention of Infection among Immunocompromised Patients: A Concise Review of Recent Systematic Reviews

by Kay Choong See

Vaccines 2022, 10(5), 800; https://doi.org/10.3390/vaccines10050800 - 18 May 2022

Cited by 26 | Viewed by 4611

Abstract

Vaccination is crucial for avoiding infection-associated morbidity and mortality among immunocompromised patients. However, immunocompromised patients respond less well to vaccinations compared to healthy people, and little is known about the relative efficacy of various vaccines among different immunocompromised states. A total of 54 [...] Read more.

Vaccination is crucial for avoiding infection-associated morbidity and mortality among immunocompromised patients. However, immunocompromised patients respond less well to vaccinations compared to healthy people, and little is known about the relative efficacy of various vaccines among different immunocompromised states. A total of 54 systematic reviews (22 COVID-19; 32 non-COVID-19) published within the last 5 years in Pubmed^® were reviewed. They demonstrated similar patterns within three seroconversion response categories: good (about >60% when compared to healthy controls), intermediate (~40–60%), and poor (about <40%). Good vaccine responses would be expected for patients with chronic kidney disease, human immunodeficiency virus infection (normal CD4 counts), immune-mediated inflammatory diseases, post-splenectomy states, and solid tumors. Intermediate vaccine responses would be expected for patients with anti-cytotoxic T-lymphocyte antigen-4 therapy, hematologic cancer, and human immunodeficiency virus infection (low CD4 counts). Poor vaccine responses would be expected for patients with B-cell-depleting agents (e.g., anti-CD20 therapy), hematopoietic stem-cell transplant, solid organ transplant, and liver cirrhosis. For all vaccine response categories, vaccination should be timed when patients are least immunosuppressed. For the intermediate and poor vaccine response categories, high-dose vaccine, revaccination when patients are less immunosuppressed, checking for seroconversion, additional booster doses, and long-acting monoclonal antibodies may be considered, supplemented by shielding measures. Full article

(This article belongs to the Special Issue Vaccines for Patients With Immunodeficiencies and Their Efficacy: An Overview in Pandemic Era)

16 pages, 1425 KiB

Open AccessEditor’s ChoiceReview

The Global Impact of Hepatitis B Vaccination on Hepatocellular Carcinoma

by Joan Ericka Flores, Alexander J. Thompson, Marno Ryan and Jessica Howell

Vaccines 2022, 10(5), 793; https://doi.org/10.3390/vaccines10050793 - 17 May 2022

Cited by 41 | Viewed by 5803

Abstract

Over 1.5 million preventable new hepatitis B infections continue to occur each year and there are an estimated 296 million people living with chronic hepatitis B infection worldwide, resulting in more than 820,000 deaths annually due to liver cirrhosis and hepatocellular carcinoma (HCC). [...] Read more.

Over 1.5 million preventable new hepatitis B infections continue to occur each year and there are an estimated 296 million people living with chronic hepatitis B infection worldwide, resulting in more than 820,000 deaths annually due to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B vaccination remains the cornerstone of public health policy to prevent HCC and a vital component of the global hepatitis B elimination response. The WHO has set a 90% vaccination target to achieve hepatitis B elimination by 2030; however, there is wide variability in reported birth dose coverage, with global coverage at only 42%. In this review, we outline the global trends in hepatitis B vaccination coverage and the impact of hepatitis B vaccination on HCC incidence and discuss the challenges and enabling factors for achieving WHO 2030 hepatitis B vaccination coverage targets. Full article

(This article belongs to the Special Issue Hepatitis and Vaccines)

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11 pages, 852 KiB

Open AccessEditor’s ChoiceReview

Uptake of COVID-19 Vaccines among Pregnant Women: A Systematic Review and Meta-Analysis

by Petros Galanis, Irene Vraka, Olga Siskou, Olympia Konstantakopoulou, Aglaia Katsiroumpa and Daphne Kaitelidou

Vaccines 2022, 10(5), 766; https://doi.org/10.3390/vaccines10050766 - 12 May 2022

Cited by 65 | Viewed by 5350

Abstract

Mass vaccination against COVID-19 is essential to control the pandemic. COVID-19 vaccines are now recommended during pregnancy to prevent adverse outcomes. With this review, we aimed to evaluate the evidence in the literature regarding the uptake of COVID-19 vaccinations among pregnant women. A [...] Read more.

Mass vaccination against COVID-19 is essential to control the pandemic. COVID-19 vaccines are now recommended during pregnancy to prevent adverse outcomes. With this review, we aimed to evaluate the evidence in the literature regarding the uptake of COVID-19 vaccinations among pregnant women. A comprehensive search was performed in PubMed, Medline, Scopus, ProQuest, Web of Science, CINAHL, and medRxiv from inception to 23 March 2022. We performed a meta-analysis to estimate the overall proportion of pregnant women vaccinated against COVID-19. We found 11 studies including 703,004 pregnant women. The overall proportion of pregnant women vaccinated against COVID-19 was 27.5% (95% CI: 18.8–37.0%). Predictors of COVID-19 vaccination uptake were older age, ethnicity, race, trust in COVID-19 vaccines, and fear of COVID-19 during pregnancy. Mistrust in the government, diagnosis of COVID-19 during pregnancy, and fears about the safety and side effects of COVID-19 vaccines were reasons for declining vaccination. The global COVID-19 vaccination prevalence in pregnant women is low. A large gap exists in the literature on the factors influencing the decision of pregnant women to be vaccinated against COVID-19. Targeted information campaigns are essential to increase vaccine literacy among pregnant women. Full article

(This article belongs to the Special Issue People’s Perception on COVID-19 Vaccine and Its Accessibility)

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33 pages, 1784 KiB

Open AccessEditor’s ChoiceReview

Vaccination against Bacterial Infections: Challenges, Progress, and New Approaches with a Focus on Intracellular Bacteria

by Anke Osterloh

Vaccines 2022, 10(5), 751; https://doi.org/10.3390/vaccines10050751 - 10 May 2022

Cited by 22 | Viewed by 7742

Abstract

Many bacterial infections are major health problems worldwide, and treatment of many of these infectious diseases is becoming increasingly difficult due to the development of antibiotic resistance, which is a major threat. Prophylactic vaccines against these bacterial pathogens are urgently needed. This is [...] Read more.

Many bacterial infections are major health problems worldwide, and treatment of many of these infectious diseases is becoming increasingly difficult due to the development of antibiotic resistance, which is a major threat. Prophylactic vaccines against these bacterial pathogens are urgently needed. This is also true for bacterial infections that are still neglected, even though they affect a large part of the world’s population, especially under poor hygienic conditions. One example is typhus, a life-threatening disease also known as “war plague” caused by Rickettsia prowazekii, which could potentially come back in a war situation such as the one in Ukraine. However, vaccination against bacterial infections is a challenge. In general, bacteria are much more complex organisms than viruses and as such are more difficult targets. Unlike comparatively simple viruses, bacteria possess a variety of antigens whose immunogenic potential is often unknown, and it is unclear which antigen can elicit a protective and long-lasting immune response. Several vaccines against extracellular bacteria have been developed in the past and are still used successfully today, e.g., vaccines against tetanus, pertussis, and diphtheria. However, while induction of antibody production is usually sufficient for protection against extracellular bacteria, vaccination against intracellular bacteria is much more difficult because effective defense against these pathogens requires T cell-mediated responses, particularly the activation of cytotoxic CD8⁺ T cells. These responses are usually not efficiently elicited by immunization with non-living whole cell antigens or subunit vaccines, so that other antigen delivery strategies are required. This review provides an overview of existing antibacterial vaccines and novel approaches to vaccination with a focus on immunization against intracellular bacteria. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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25 pages, 1469 KiB

Open AccessEditor’s ChoiceReview

Cell Lines for the Development of African Swine Fever Virus Vaccine Candidates: An Update

by Dionigia Meloni, Giulia Franzoni and Annalisa Oggiano

Vaccines 2022, 10(5), 707; https://doi.org/10.3390/vaccines10050707 - 29 Apr 2022

Cited by 22 | Viewed by 5064

Abstract

African swine fever virus (ASFV) is the etiological agent of a highly lethal disease in both domestic and wild pigs. The virus has rapidly spread worldwide and has no available licensed vaccine. An obstacle to the construction of a safe and efficient vaccine [...] Read more.

African swine fever virus (ASFV) is the etiological agent of a highly lethal disease in both domestic and wild pigs. The virus has rapidly spread worldwide and has no available licensed vaccine. An obstacle to the construction of a safe and efficient vaccine is the lack of a suitable cell line for ASFV isolation and propagation. Macrophages are the main targets for ASFV, and they have been widely used to study virus–host interactions; nevertheless, obtaining these cells is time-consuming and expensive, and they are not ethically suitable for the production of large-scale vaccines. To overcome these issues, different virulent field isolates have been adapted on monkey or human continuous cells lines; however, several culture passages often lead to significant genetic modifications and the loss of immunogenicity of the adapted strain. Thus, several groups have attempted to establish a porcine cell line able to sustain ASFV growth. Preliminary data suggested that some porcine continuous cell lines might be an alternative to primary macrophages for ASFV research and for large-scale vaccine production, although further studies are still needed. In this review, we summarize the research to investigate the most suitable cell line for ASFV isolation and propagation. Full article

(This article belongs to the Special Issue African Swine Fever Immunity and Vaccines)

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13 pages, 2207 KiB

Open AccessEditor’s ChoiceArticle

Internal and External Motivations and Risk Perception toward COVID-19 Vaccination in Adolescents in the U.S.

by Pikuei Tu, Michaela Kotarba, Brooke Bier, Rachel Clark and Cheryl Lin

Vaccines 2022, 10(5), 697; https://doi.org/10.3390/vaccines10050697 - 29 Apr 2022

Cited by 17 | Viewed by 3238

Abstract

The COVID-19 vaccine is widely available to adolescents in the U.S.; however, vaccine hesitancy poses a threat to full coverage. The literature shows that perceived risks and the presence or lack of motivators are determinants for vaccination decisions, yet research evidence from minors [...] Read more.

The COVID-19 vaccine is widely available to adolescents in the U.S.; however, vaccine hesitancy poses a threat to full coverage. The literature shows that perceived risks and the presence or lack of motivators are determinants for vaccination decisions, yet research evidence from minors is scant. This study adopted the Protection Motivation framework to identify differences in these facilitators and compare the influence of internal and external motivators among American adolescents in COVID-19 vaccine uptake. A nationwide online survey analyzed 13–17-year-old teenagers’ COVID-19 beliefs as well as present or potential reasons for accepting the vaccine. Of the 439 participants, 21.18% were not and did not plan to get vaccinated. Another 52.39% had at least one dosage, of which over three-quarters were internally motivated (whereas those unvaccinated were more likely to be externally motivated, X² = 4.117, p = 0.042). In unvaccinated individuals, older adolescents reported slightly more internal motivators than younger adolescents (t = −2.023, p = 0.046). Internal motivation was associated with higher risk perception (r² = 0.06651, p = 0.001), but risk perception had a stronger relationship with vaccination status (r² = 0.1816, p < 0.001), with vaccinated individuals showing higher risk perception than those unvaccinated (mean difference = 0.42 on a scale of 1–4; t = −3.603, p < 0.001); the risk perception difference was even greater between hesitant and non-hesitant participants (mean difference = 0.63; t = −0.892, p < 0.001). The relationship was moderated by perceived knowledge, where the difference in risk perception between vaccination status was only significant for those with low perceived knowledge (f = 10.59, p = 0.001). Increasing awareness of disease risks and stressing internal motivators may be key to improving uptake in young people. Future research could delve deeper into risk perception formation of adolescents and why and how it differs across populations. Full article

(This article belongs to the Special Issue Feature Papers of Vaccines and Society)

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14 pages, 657 KiB

Open AccessEditor’s ChoiceArticle

COVID-19 Vaccination in Multiple Sclerosis and Inflammatory Diseases: Effects from Disease-Modifying Therapy, Long-Term Seroprevalence and Breakthrough Infections

by Dejan Jakimovski, Karen Zakalik, Samreen Awan, Katelyn S. Kavak, Penny Pennington, David Hojnacki, Channa Kolb, Alexis A. Lizarraga, Svetlana P. Eckert, Rosila Sarrosa, Kamath Vineetha, Keith Edwards and Bianca Weinstock-Guttman

Vaccines 2022, 10(5), 695; https://doi.org/10.3390/vaccines10050695 - 28 Apr 2022

Cited by 20 | Viewed by 4030

Abstract

Background: To determine the effect of disease-modifying therapies (DMT) on humoral postvaccine seroconversion, long-term humoral response, and breakthrough COVID-19 infections in persons with multiple sclerosis (PwMS) and other neuroinflammatory disorders. Methods: A total of 757 PwMS and other neuroinflammatory disorders were recruited in [...] Read more.

Background: To determine the effect of disease-modifying therapies (DMT) on humoral postvaccine seroconversion, long-term humoral response, and breakthrough COVID-19 infections in persons with multiple sclerosis (PwMS) and other neuroinflammatory disorders. Methods: A total of 757 PwMS and other neuroinflammatory disorders were recruited in two MS centers and vaccinated with one of the FDA-approved vaccines (BNT162b2, mRNA-1273, Ad26.COV2.S). The primary outcomes are the rate of humoral postvaccine seroconversion and anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immunoglobulin G (IgG) differences between patients on different DMTs. Secondary measures include breakthrough infections and humoral response after six months. Other outcomes include differences in vaccine response between SARS-CoV-2 vaccines and the effects of age and comorbidities on the vaccine response. Results: A total of 465 (68.4%) PwMS and 55 (74.3%) patients with neuroinflammatory diseases were seropositive at 4–12 weeks after vaccination. A significant difference in seroconversion based on the DMT used at the time of vaccination (p < 0.001) was observed, with the lowest rates seen in patients treated with anti-CD20 antibodies (23.2%) and sphingosine-1-phosphate modulators (S1P) (30.8%). In seropositive patients, there was a significant decrease in anti-SARS IgG from mean 20.0 to 4.7 at six months (p = 0.004). Thirty-nine patients had breakthrough infection, but only two seronegative patients required hospitalization. mRNA vaccines resulted in significantly greater seroconversion compared to Ad26.COV2.S (p < 0.001). Older age and presence of cardiovascular comorbidities were associated with lower anti-SARS IgG (p = 0.021 and p = 0.003, respectively) Conclusions: PwMS and neuroinflammatory disorders treated with anti-CD20 and S1P medications have lower humoral response after anti-SARS-CoV-2 vaccination, even after booster dose. Waning of the humoral response puts vaccinated PwMS at a greater risk of COVID-19 breakthrough. Full article

(This article belongs to the Special Issue Vaccine-Induced Reprogramming of Innate Immune Response)

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28 pages, 2249 KiB

Open AccessEditor’s ChoiceReview

COVID-19 Vaccines: Current and Future Perspectives

by Luca Soraci, Fabrizia Lattanzio, Giulia Soraci, Maria Elsa Gambuzza, Claudio Pulvirenti, Annalisa Cozza, Andrea Corsonello, Filippo Luciani and Giovanni Rezza

Vaccines 2022, 10(4), 608; https://doi.org/10.3390/vaccines10040608 - 13 Apr 2022

Cited by 35 | Viewed by 8023

Abstract

Currently available vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are highly effective but not able to keep the coronavirus disease 2019 (COVID-19) pandemic completely under control. Alternative R&D strategies are required to induce a long-lasting immunological response and to reduce adverse events [...] Read more.

Currently available vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are highly effective but not able to keep the coronavirus disease 2019 (COVID-19) pandemic completely under control. Alternative R&D strategies are required to induce a long-lasting immunological response and to reduce adverse events as well as to favor rapid development and large-scale production. Several technological platforms have been used to develop COVID-19 vaccines, including inactivated viruses, recombinant proteins, DNA- and RNA-based vaccines, virus-vectored vaccines, and virus-like particles. In general, mRNA vaccines, protein-based vaccines, and vectored vaccines have shown a high level of protection against COVID-19. However, the mutation-prone nature of the spike (S) protein affects long-lasting vaccine protection and its effectiveness, and vaccinated people can become infected with new variants, also showing high virus levels. In addition, adverse effects may occur, some of them related to the interaction of the S protein with the angiotensin-converting enzyme 2 (ACE-2). Thus, there are some concerns that need to be addressed and challenges regarding logistic problems, such as strict storage at low temperatures for some vaccines. In this review, we discuss the limits of vaccines developed against COVID-19 and possible innovative approaches. Full article

(This article belongs to the Special Issue Vaccination Strategies for COVID-19)

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22 pages, 1334 KiB

Open AccessEditor’s ChoiceReview

Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change

by Tamas Fulop, Anis Larbi, Graham Pawelec, Alan A. Cohen, Guillaume Provost, Abedelouahed Khalil, Guy Lacombe, Serafim Rodrigues, Mathieu Desroches, Katsuiku Hirokawa, Claudio Franceschi and Jacek M. Witkowski

Vaccines 2022, 10(4), 607; https://doi.org/10.3390/vaccines10040607 - 13 Apr 2022

Cited by 27 | Viewed by 6410

Abstract

Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine [...] Read more.

Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine failure is seasonal influenza, but, while it is usually the case that the efficiency of this vaccine is lower in older than younger adults, this is not always true, and the reasons for the differential responses are manifold. Undoubtedly, changes in the innate and adaptive immune response with ageing are associated with failure to respond to the influenza vaccine, but the cause is unclear. Moreover, recent advances in vaccine formulations and adjuvants, as well as in our understanding of immune changes with ageing, have contributed to the development of vaccines, such as those against herpes zoster and SARS-CoV-2, that can protect against serious disease in older adults just as well as in younger people. In the present article, we discuss the reasons why it is a myth that vaccines inevitably protect less well in older individuals, and that vaccines represent one of the most powerful means to protect the health and ensure the quality of life of older adults. Full article

(This article belongs to the Special Issue Knowledge about Vaccines and Vaccination in Older People)

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23 pages, 2505 KiB

Open AccessEditor’s ChoiceArticle

Protective CD8+ T Cell Response Induced by Modified Vaccinia Virus Ankara Delivering Ebola Virus Nucleoprotein

by Alexandra Kupke, Asisa Volz, Erik Dietzel, Astrid Freudenstein, Jörg Schmidt, Hosam Shams-Eldin, Sylvia Jany, Lucie Sauerhering, Verena Krähling, Michelle Gellhorn Serra, Christiane Herden, Markus Eickmann, Stephan Becker and Gerd Sutter

Vaccines 2022, 10(4), 533; https://doi.org/10.3390/vaccines10040533 - 29 Mar 2022

Cited by 10 | Viewed by 3774

Abstract

The urgent need for vaccines against Ebola virus (EBOV) was underscored by the large outbreak in West Africa (2014–2016). Since then, several promising vaccine candidates have been tested in pre-clinical and clinical studies. As a result, two vaccines were approved for human use [...] Read more.

The urgent need for vaccines against Ebola virus (EBOV) was underscored by the large outbreak in West Africa (2014–2016). Since then, several promising vaccine candidates have been tested in pre-clinical and clinical studies. As a result, two vaccines were approved for human use in 2019/2020, of which one includes a heterologous adenovirus/Modified Vaccinia virus Ankara (MVA) prime-boost regimen. Here, we tested new vaccine candidates based on the recombinant MVA vector, encoding the EBOV nucleoprotein (MVA-EBOV-NP) or glycoprotein (MVA-EBOV-GP) for their efficacy after homologous prime-boost immunization in mice. Our aim was to investigate the role of each antigen in terms of efficacy and correlates of protection. Sera of mice vaccinated with MVA-EBOV-GP were virus-neutralizing and MVA-EBOV-NP immunization readily elicited interferon-γ-producing NP-specific CD8+ T cells. While mock-vaccinated mice succumbed to EBOV infection, all vaccinated mice survived and showed drastically decreased viral loads in sera and organs. In addition, MVA-EBOV-NP vaccinated mice became susceptible to lethal EBOV infection after depletion of CD8+ T cells prior to challenge. This study highlights the potential of MVA-based vaccines to elicit humoral immune responses as well as a strong and protective CD8+ T cell response and contributes to understanding the possible underlying mechanisms. Full article

(This article belongs to the Special Issue A Modern Take on Replicating Viral Vaccines)

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10 pages, 916 KiB

Open AccessEditor’s ChoiceArticle

Humoral Response after Three Doses of mRNA-1273 or BNT162b2 SARS-CoV-2 Vaccines in Hemodialysis Patients

by José Jesús Broseta, Diana Rodríguez-Espinosa, Elena Cuadrado, Néstor Rodríguez, José Luis Bedini and Francisco Maduell

Vaccines 2022, 10(4), 522; https://doi.org/10.3390/vaccines10040522 - 27 Mar 2022

Cited by 13 | Viewed by 3378

Abstract

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline [...] Read more.

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non- or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters. Full article

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21 pages, 6487 KiB

Open AccessEditor’s ChoiceArticle

Comparative Reverse Vaccinology of Piscirickettsia salmonis, Aeromonas salmonicida, Yersinia ruckeri, Vibrio anguillarum and Moritella viscosa, Frequent Pathogens of Atlantic Salmon and Lumpfish Aquaculture

by Joy Chukwu-Osazuwa, Trung Cao, Ignacio Vasquez, Hajarooba Gnanagobal, Ahmed Hossain, Vimbai Irene Machimbirike and Javier Santander

Vaccines 2022, 10(3), 473; https://doi.org/10.3390/vaccines10030473 - 18 Mar 2022

Cited by 19 | Viewed by 5090

Abstract

Marine finfish aquaculture is affected by diverse infectious diseases, and they commonly occur as co-infection. Some of the most frequent and prevalent Gram-negative bacterial pathogens of the finfish aquaculture include Piscirickettsia salmonis, Aeromonas salmonicida, Yersinia ruckeri, Vibrio anguillarum and Moritella [...] Read more.

Marine finfish aquaculture is affected by diverse infectious diseases, and they commonly occur as co-infection. Some of the most frequent and prevalent Gram-negative bacterial pathogens of the finfish aquaculture include Piscirickettsia salmonis, Aeromonas salmonicida, Yersinia ruckeri, Vibrio anguillarum and Moritella viscosa. To prevent co-infections in aquaculture, polyvalent or universal vaccines would be ideal. Commercial polyvalent vaccines against some of these pathogens are based on whole inactivated microbes and their efficacy is controversial. Identification of common antigens can contribute to the development of effective universal or polyvalent vaccines. In this study, we identified common and unique antigens of P. salmonis, A. salmonicida, Y. ruckeri, V. anguillarum and M. viscosa based on a reverse vaccinology pipeline. We screened the proteome of several strains using complete available genomes and identified a total of 154 potential antigens, 74 of these identified antigens corresponded to secreted proteins, and 80 corresponded to exposed outer membrane proteins (OMPs). Further analysis revealed the outer membrane antigens TonB-dependent siderophore receptor, OMP assembly factor BamA, the LPS assembly protein LptD and secreted antigens flagellar hook assembly protein FlgD and flagellar basal body rod protein FlgG are present in all pathogens used in this study. Sequence and structural alignment of these antigens showed relatively low percentage sequence identity but good structural homology. Common domains harboring several B-cells and T-cell epitopes binding to major histocompatibility (MHC) class I and II were identified. Selected peptides were evaluated for docking with Atlantic salmon (Salmo salar) and Lumpfish MHC class II. Interaction of common peptide-MHC class II showed good in-silico binding affinities and dissociation constants between −10.3 to −6.5 kcal mol⁻¹ and 5.10 × 10⁻⁹ to 9.4 × 10⁻⁶ M. This study provided the first list of antigens that can be used for the development of polyvalent or universal vaccines against these Gram-negative bacterial pathogens affecting finfish aquaculture. Full article

(This article belongs to the Special Issue Vaccines for Aquaculture)

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14 pages, 331 KiB

Open AccessEditor’s ChoiceReview

Utilization of Viral Vector Vaccines in Preparing for Future Pandemics

by Kimberly A. Hofmeyer, Katherine M. Bianchi and Daniel N. Wolfe

Vaccines 2022, 10(3), 436; https://doi.org/10.3390/vaccines10030436 - 12 Mar 2022

Cited by 12 | Viewed by 4304

Abstract

As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks [...] Read more.

As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics. Full article

(This article belongs to the Special Issue A Modern Take on Replicating Viral Vaccines)

13 pages, 456 KiB

Open AccessEditor’s ChoiceReview

Roles of the Tol/Pal System in Bacterial Pathogenesis and Its Application to Antibacterial Therapy

by Hidetada Hirakawa, Kazutomo Suzue and Haruyoshi Tomita

Vaccines 2022, 10(3), 422; https://doi.org/10.3390/vaccines10030422 - 10 Mar 2022

Cited by 11 | Viewed by 5176

Abstract

The Tol/Pal system (also written as “The Tol-Pal system”) is a set of protein complexes produced by most Gram-negative bacteria. It comprises the inner membrane-associated and the outer membrane-anchored subunits composed of the TolA, TolQ, and TolR proteins and the TolB and Pal [...] Read more.

The Tol/Pal system (also written as “The Tol-Pal system”) is a set of protein complexes produced by most Gram-negative bacteria. It comprises the inner membrane-associated and the outer membrane-anchored subunits composed of the TolA, TolQ, and TolR proteins and the TolB and Pal proteins, respectively. Although the Tol/Pal system was first defined as bacterial proteins involved in colicin uptake of Escherichia coli, its global roles have been characterized in several studies as mentioned in this article. Pathogenesis of many Gram-negative pathogens is sustained by the Tol/Pal system. It is also essential for cell growth and fitness in some pathogens. Therefore, the Tol/Pal system is proposed as a potential target for antimicrobial chemotherapy. Although the tol/pal mutants are low in virulence, they still have the ability to stimulate the immune system. The Pal protein is highly immunogenic and induces both adaptive and innate immune responses. Therefore, the tol/pal mutant strains and Pal proteins also have potential vaccine properties. For these reasons, the Tol/Pal system represents a promising research target in the development of antibacterial therapeutic strategies for refractory infections caused by multi-drug-resistant (MDR), Gram-negative pathogens. In this paper, we summarize studies on the Tol/Pal system associated with bacterial pathogenesis and vaccine development. Full article

(This article belongs to the Special Issue Development of Attenuated Vaccine)

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14 pages, 583 KiB

Open AccessEditor’s ChoiceReview

Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data: A Systematic Review

by Megumi Kurosawa, Masayuki Sekine, Manako Yamaguchi, Risa Kudo, Sharon J. B. Hanley, Megumi Hara, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Sayaka Ikeda, Asami Yagi and Takayuki Enomoto

Vaccines 2022, 10(2), 256; https://doi.org/10.3390/vaccines10020256 - 8 Feb 2022

Cited by 7 | Viewed by 8084

Abstract

The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and [...] Read more.

The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and real-world data. As far as we searched, the longest period of preventive effect for the bivalent, 4-valent, and 9-valent vaccine were 11 years in the Costa Rica trial, 14 years in the FUTURE II, and 8 years in the LTFU extension study of V503-002 and the Scandinavian study, respectively. The sustained clinical effect during the observation period was longest for the 4-valent vaccine. In real-world data, the longest observation period of the vaccine effectiveness was 12 years in an Australian study for the 4-valent vaccine. On the other hand, the longest period of long-term persistence of HPV vaccine-induced seropositivity was 14 years in FUTURE II for the 4-valent vaccine. For the bivalent vaccine, additional long-term follow-up studies may not have been planned due to the launch of the 4-valent and 9-valent vaccines. In some studies of the 9-valent vaccine, the results have not yet been published because of the short observation period. The additional results are expected in the future. In a national immunization program, most girls and boys are inoculated with HPV vaccine by the time puberty begins; thus, it is important to monitor the vaccine effect at least until the sexually active period in their 20s and 30s. Full article

(This article belongs to the Special Issue Epidemiological Studies of HPV Infection and Vaccination)

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13 pages, 275 KiB

Open AccessEditor’s ChoiceArticle

Tipping the Fencesitters—The Impact of a Minimal Intervention Enhanced with Biological Facts on Swiss Student Teachers’ Perception of HPV Vaccination Safety

by Alla Keselman and Albert Zeyer

Vaccines 2022, 10(2), 175; https://doi.org/10.3390/vaccines10020175 - 23 Jan 2022

Cited by 6 | Viewed by 3392

Abstract

Not much is known about the role of scientific knowledge in vaccination decision making. This study is based on previous findings that the concern about the human papillomavirus (HPV) agent mutating back to a virulent HPV was common among Swiss student teachers and [...] Read more.

Not much is known about the role of scientific knowledge in vaccination decision making. This study is based on previous findings that the concern about the human papillomavirus (HPV) agent mutating back to a virulent HPV was common among Swiss student teachers and turned out to be one factor of vaccine hesitancy. The study investigate the impact of a standard public health brochure describing the effectiveness, safety, and importance of HPV vaccination on young student teachers, and the additional effect of supplementing the standard brochure with biological arguments against the mutation concerns. It uses a pre-posttest design and assigns participants randomly to two groups, one reviewing a standard public health brochure, the other the same brochure enhanced with additional biological information. Participants in both groups showed a significant positive change in their beliefs about vaccination safety, effectiveness, and importance in preventing cervical cancer. Post hoc analysis showed significant safety beliefs gain for the subgroup of participants who received the biology-enhanced text and held moderate, rather than high or low, pretest safety beliefs—the so-called fencesitters. We conclude that these fencesitters may particularly profit from even minimal (biologically supplemented) interventions, an effect that should receive more attention in future research. Full article

(This article belongs to the Special Issue Vaccine Hesitancy and Child Immunizations: Rationales, Issues and Knowledge Gaps 2.0)

10 pages, 1499 KiB

Open AccessEditor’s ChoiceArticle

Reduced Titers of Circulating Anti-SARS-CoV-2 Antibodies and Risk of COVID-19 Infection in Healthcare Workers during the Nine Months after Immunization with the BNT162b2 mRNA Vaccine

by Luca Coppeta, Cristiana Ferrari, Giuseppina Somma, Andrea Mazza, Umberto D’Ancona, Fabbio Marcuccilli, Sandro Grelli, Marco Trabucco Aurilio, Antonio Pietroiusti, Andrea Magrini and Stefano Rizza

Vaccines 2022, 10(2), 141; https://doi.org/10.3390/vaccines10020141 - 18 Jan 2022

Cited by 36 | Viewed by 3835

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact on health services; hundreds of thousands of healthcare workers (HCWs) have died from coronavirus disease 2019 (COVID-19). The introduction of the BNT162b2 mRNA vaccine in Italy provided recipients with [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact on health services; hundreds of thousands of healthcare workers (HCWs) have died from coronavirus disease 2019 (COVID-19). The introduction of the BNT162b2 mRNA vaccine in Italy provided recipients with significant protection against COVID-19 within one to two weeks after the administration of the second of the two recommended doses. While the vaccine induces a robust T cell response, the protective role of factors and pathways other than those related to memory B cell responses to specific SARS-CoV-2 antigens remains unclear. This retrospective study aimed to evaluate the determinants of serological protection in a group of vaccinated HCWs (n = 793) by evaluating circulating levels of antiviral spike receptor-binding domain (S-RBD) antibodies during the nine-month period following vaccination. We found that 99.5% of the HCWs who received the two doses of the BNT162b2 vaccine developed protective antibodies that were maintained at detectable levels for as long as 250 days after the second dose of the vaccine. Multivariate analysis was performed on anti-S-RBD titers in a subgroup of participants (n = 173) that were evaluated twice during this period. The results of this analysis reveal that the antibody titer observed at the second time point was significantly related to the magnitude of the primary response, the time that had elapsed between the first and the second evaluation, and a previous history of SARS-CoV-2 infection. Of importance is the finding that despite waning antibody titers following vaccination, none of the study participants contracted severe COVID-19 during the observational period. Full article

(This article belongs to the Special Issue Feature Papers of Epidemiology and Vaccines)

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9 pages, 209 KiB

Open AccessEditor’s ChoiceReview

Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin

by Claudio Costantini, Frank L. van de Veerdonk and Luigina Romani

Vaccines 2020, 8(4), 713; https://doi.org/10.3390/vaccines8040713 - 1 Dec 2020

Cited by 26 | Viewed by 4539

Abstract

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical factor in the clinical presentation of COVID-19, which may range from asymptomatic to a fatal, multi-organ disease. A dysregulated immune response not only compromises the ability of the host [...] Read more.

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical factor in the clinical presentation of COVID-19, which may range from asymptomatic to a fatal, multi-organ disease. A dysregulated immune response not only compromises the ability of the host to resolve the viral infection, but may also predispose the individual to secondary bacterial and fungal infections, a risk to which the current therapeutic immunomodulatory approaches significantly contribute. Among the secondary infections that may occur in COVID-19 patients, coronavirus-associated pulmonary aspergillosis (CAPA) is emerging as a potential cause of morbidity and mortality, although many aspects of the disease still remain unresolved. With this opinion, we present the current view of CAPA and discuss how the same mechanisms that underlie the dysregulated immune response in COVID-19 increase susceptibility to Aspergillus infection. Likewise, resorting to endogenous pathways of immunomodulation may not only restore immune homeostasis in COVID-19 patients, but also reduce the risk for aspergillosis. Therefore, CAPA represents the other side of the coin in COVID-19 and our advances in the understanding and treatment of the immune response in COVID-19 should represent the framework for the study of CAPA. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

14 pages, 1756 KiB

Open AccessEditor’s ChoiceArticle

Influences on Attitudes Regarding Potential COVID-19 Vaccination in the United States

by Kendall Pogue, Jamie L. Jensen, Carter K. Stancil, Daniel G. Ferguson, Savannah J. Hughes, Emily J. Mello, Ryan Burgess, Bradford K. Berges, Abraham Quaye and Brian D. Poole

Vaccines 2020, 8(4), 582; https://doi.org/10.3390/vaccines8040582 - 3 Oct 2020

Cited by 379 | Viewed by 30421

Abstract

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large [...] Read more.

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. The aim of this study was to understand the attitudes towards and obstacles facing vaccination with a potential COVID-19 vaccine. To measure these attitudes a survey was administered to 316 respondents across the United States by a survey corporation. Structural equation modeling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short- and long-term side effects before a vaccine is released. Full article

(This article belongs to the Special Issue Vaccination and Public Health: Optimizing Vaccine Uptake through the Application of Social and Behavioral Science Theory, Principles, and Strategies)

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11 pages, 523 KiB

Open AccessEditor’s ChoiceArticle

Relationship between Citizens’ Health Engagement and Intention to Take the COVID-19 Vaccine in Italy: A Mediation Analysis

by Guendalina Graffigna, Lorenzo Palamenghi, Stefania Boccia and Serena Barello

Vaccines 2020, 8(4), 576; https://doi.org/10.3390/vaccines8040576 - 1 Oct 2020

Cited by 137 | Viewed by 10360

Abstract

The actual effectiveness of the still-to-come vaccination against the coronavirus SARS-CoV-2 might be challenged by vaccine hesitancy, a rather common and known phenomenon whose psychological predictors are, nevertheless, still largely debated. Our study aims at understanding how adult citizens’ health engagement, perceived COVID-19 [...] Read more.

The actual effectiveness of the still-to-come vaccination against the coronavirus SARS-CoV-2 might be challenged by vaccine hesitancy, a rather common and known phenomenon whose psychological predictors are, nevertheless, still largely debated. Our study aims at understanding how adult citizens’ health engagement, perceived COVID-19 susceptibility and severity, and general vaccine-related attitudes affect the willingness to vaccinate against COVID-19. To that end, on a sample of Italian citizens, we implemented a path model to test the impact of health engagement on the willingness to vaccinate against SARS-CoV-2, and whether this relationship is direct or mediated by the general attitude towards vaccines and the risk perception. Moreover, we tested the configural and weak invariance of the model across gender and three age groups. Results show that health engagement is positively related to the intention to vaccinate and that this relationship is partially mediated by the general attitude towards vaccines. The model appears invariant across genders and partially invariant across age groups, showing some differences in the role of perceived susceptibility. These findings vouch for the implementation of educational campaigns aimed at sustaining future vaccination programs that also include health engagement promotion. Full article

(This article belongs to the Special Issue Vaccine Hesitancy and Child Immunizations: Rationales, Issues and Knowledge Gaps)

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14 pages, 864 KiB

Open AccessEditor’s ChoiceArticle

Acceptance of COVID-19 Vaccination during the COVID-19 Pandemic in China

by Jiahao Wang, Rize Jing, Xiaozhen Lai, Haijun Zhang, Yun Lyu, Maria Deloria Knoll and Hai Fang

Vaccines 2020, 8(3), 482; https://doi.org/10.3390/vaccines8030482 - 27 Aug 2020

Cited by 686 | Viewed by 51076

Abstract

Background: Faced with the coronavirus disease 2019 (COVID-19) pandemic, the development of COVID-19 vaccines has been progressing at an unprecedented rate. This study aimed to evaluate the acceptance of COVID-19 vaccination in China and give suggestions for vaccination strategies and immunization programs accordingly. [...] Read more.

Background: Faced with the coronavirus disease 2019 (COVID-19) pandemic, the development of COVID-19 vaccines has been progressing at an unprecedented rate. This study aimed to evaluate the acceptance of COVID-19 vaccination in China and give suggestions for vaccination strategies and immunization programs accordingly. Methods: In March 2020, an anonymous cross-sectional survey was conducted online among Chinese adults. The questionnaire collected socio-demographic characteristics, risk perception, the impact of COVID-19, attitudes, acceptance and attribute preferences of vaccines against COVID-19 during the pandemic. Multivariate logistic regression was performed to identify the influencing factors of vaccination acceptance. Results: Of the 2058 participants surveyed, 1879 (91.3%) stated that they would accept COVID-19 vaccination after the vaccine becomes available, among whom 980 (52.2%) wanted to get vaccinated as soon as possible, while others (47.8%) would delay the vaccination until the vaccine’s safety was confirmed. Participants preferred a routine immunization schedule (49.4%) to emergency vaccination (9.0%) or either of them (41.6%). Logistic regression showed that being male, being married, perceiving a high risk of infection, being vaccinated against influenza in the past season, believing in the efficacy of COVID-19 vaccination or valuing doctor’s recommendations could increase the probability of accepting COVID-19 vaccination as soon as possible, while having confirmed or suspected cases in local areas, valuing vaccination convenience or vaccine price in decision-making could hinder participants from immediate vaccination. Conclusion: During the pandemic period, a strong demand for and high acceptance of COVID-19 vaccination has been shown among the Chinese population, while concerns about vaccine safety may hinder the promotion of vaccine uptake. To expand vaccination coverage, immunization programs should be designed to remove barriers in terms of vaccine price and vaccination convenience, and health education and communication from authoritative sources are important ways to alleviate public concerns about vaccine safety. Full article

(This article belongs to the Special Issue Vaccination and Public Health: Optimizing Vaccine Uptake through the Application of Social and Behavioral Science Theory, Principles, and Strategies)

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10 pages, 1596 KiB

Open AccessEditor’s ChoiceCommunication

Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth

by Nathifa Moyo, Edmund G. Wee, Bette Korber, Kapil Bahl, Samantha Falcone, Sunny Himansu, Adrianne L. Wong, Antu K. Dey, Mark Feinberg and Tomáš Hanke

Vaccines 2020, 8(3), 360; https://doi.org/10.3390/vaccines8030360 - 6 Jul 2020

Cited by 17 | Viewed by 10830

Abstract

A vaccine will likely be one of the key tools for ending the HIV-1/AIDS epidemic by preventing HIV-1 spread within uninfected populations and achieving a cure for people living with HIV-1. The currently prevailing view of the vaccine field is to introduce protective [...] Read more.

A vaccine will likely be one of the key tools for ending the HIV-1/AIDS epidemic by preventing HIV-1 spread within uninfected populations and achieving a cure for people living with HIV-1. The currently prevailing view of the vaccine field is to introduce protective antibodies, nevertheless, a vaccine to be effective may need to harness protective T cells. We postulated that focusing a T-cell response on the most vulnerable regions of the HIV-1 proteome while maximizing a perfect match between the vaccine and circulating viruses will control HIV-1 replication. We currently use a combination of replication-deficient simian (chimpanzee) adenovirus and poxvirus modified vaccinia virus Ankara to deliver bivalent conserved-mosaic immunogens to human volunteers. Here, we exploit the mRNA platform by designing tetravalent immunogens designated as HIVconsvM, and demonstrate that mRNA formulated in lipid nanoparticles induces potent, broad and polyfunctional T-cell responses in a pre-clinical model. These results support optimization and further development of this vaccine strategy in experimental medicine trials in humans. Full article

(This article belongs to the Section HIV Vaccines)

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13 pages, 2636 KiB

Open AccessEditor’s ChoiceArticle

Yeast-Based Aβ1-15 Vaccine Elicits Strong Immunogenicity and Attenuates Neuropathology and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice

by Dong-qun Liu, Shuai Lu, Lun Zhang, Ya-ru Huang, Mei Ji, Xiao-ying Sun, Xiao-ge Liu and Rui-tian Liu

Vaccines 2020, 8(3), 351; https://doi.org/10.3390/vaccines8030351 - 1 Jul 2020

Cited by 11 | Viewed by 4453

Abstract

Immunotherapy focusing on reducing the amyloid-beta (Aβ) burden is a promising treatment strategy for Alzheimer’s disease (AD). Many clinical studies on AD immunotherapies have failed due to low safety and efficacy, calling for a highly potent AD vaccine which induces sufficient antibody titer [...] Read more.

Immunotherapy focusing on reducing the amyloid-beta (Aβ) burden is a promising treatment strategy for Alzheimer’s disease (AD). Many clinical studies on AD immunotherapies have failed due to low safety and efficacy, calling for a highly potent AD vaccine which induces sufficient antibody titer while avoiding side effects. Here, we designed a yeast-based vaccine Y-5A15 comprising five copies of Aβ1-15 displayed on the surface of yeast cell wall, and we subcutaneously immunized APP/PS1 mice three times. Our results demonstrated that the Y-5A15 remarkably enhanced the Aβ epitope immunogenicity and elicited high antibody titers against Aβ in AD mice. Importantly, Y-5A15 vaccination successfully reduced Aβ levels, plaque burden and glial activation, rescued synaptic deficits and significantly ameliorated memory and cognitive decline in APP/PS1 transgenic mice, suggesting that the yeast-based Aβ epitope vaccine has a promising potency for the treatment of AD. Full article

(This article belongs to the Special Issue Human Leukocyte Antigen (HLA) and Vaccines)

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15 pages, 2692 KiB

Open AccessEditor’s ChoiceArticle

Remodeling of the Histoplasma Capsulatum Membrane Induced by Monoclonal Antibodies

by Meagan C. Burnet, Daniel Zamith-Miranda, Heino M. Heyman, Karl K. Weitz, Erin L. Bredeweg, Joshua D. Nosanchuk and Ernesto S. Nakayasu

Vaccines 2020, 8(2), 269; https://doi.org/10.3390/vaccines8020269 - 2 Jun 2020

Cited by 9 | Viewed by 5015

Abstract

Antibodies play a central role in host immunity by directly inactivating or recognizing an invading pathogen to enhance different immune responses to combat the invader. However, the cellular responses of pathogens to the presence of antibodies are not well-characterized. Here, we used different [...] Read more.

Antibodies play a central role in host immunity by directly inactivating or recognizing an invading pathogen to enhance different immune responses to combat the invader. However, the cellular responses of pathogens to the presence of antibodies are not well-characterized. Here, we used different mass spectrometry techniques to study the cellular responses of the pathogenic fungus Histoplasma capsulatum to monoclonal antibodies (mAb) against HSP60, the surface protein involved in infection. A proteomic analysis of H. capsulatum yeast cells revealed that mAb binding regulates a variety of metabolic and signaling pathways, including fatty acid metabolism, sterol metabolism, MAPK signaling and ubiquitin-mediated proteolysis. The regulation of the fatty acid metabolism was accompanied by increases in the level of polyunsaturated fatty acids, which further augmented the degree of unsaturated lipids in H. capsulatum’s membranes and energy storage lipids, such as triacylglycerols, phosphatidylcholines, phosphatidylethanolamines and phosphatidylinositols. MAb treatment also regulated sterol metabolism by increasing the levels of cholesterol and ergosterol in the cells. We also showed that global changes in the lipid profiles resulted in an increased susceptibility of H. capsulatum to the ergosterol-targeting drug amphotericin B. Overall, our data showed that mAb induction of global changes in the composition of H. capsulatum membranes can potentially impact antifungal treatment during histoplasmosis. Full article

(This article belongs to the Section Pathogens-host Immune Interface)

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20 pages, 16511 KiB

Open AccessEditor’s ChoiceArticle

Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus

by Elisa S. Roesti, Christina N. Boyle, Daniel T. Zeman, Marcos Sande-Melon, Federico Storni, Gustavo Cabral-Miranda, Alexander Knuth, Thomas A. Lutz, Monique Vogel and Martin F. Bachmann

Vaccines 2020, 8(1), 116; https://doi.org/10.3390/vaccines8010116 - 2 Mar 2020

Cited by 19 | Viewed by 6902

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These—originally β-cell secretory [...] Read more.

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These—originally β-cell secretory products—extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function. Full article

(This article belongs to the Special Issue Genomic Medicine and Advances in Vaccine Technology and Development in the Developing and Developed World)

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33 pages, 3568 KiB

Open AccessEditor’s ChoiceReview

Anti-Leishmanial Vaccines: Assumptions, Approaches, and Annulments

by Shubhranshu Zutshi, Sunil Kumar, Prashant Chauhan, Yashwant Bansode, Arathi Nair, Somenath Roy, Arup Sarkar and Bhaskar Saha

Vaccines 2019, 7(4), 156; https://doi.org/10.3390/vaccines7040156 - 18 Oct 2019

Cited by 30 | Viewed by 7121

Abstract

Leishmaniasis is a neglected protozoan parasitic disease that occurs in 88 countries but a vaccine is unavailable. Vaccination with live, killed, attenuated (physically or genetically) Leishmania have met with limited success, while peptide-, protein-, or DNA-based vaccines showed promise only in animal models. [...] Read more.

Leishmaniasis is a neglected protozoan parasitic disease that occurs in 88 countries but a vaccine is unavailable. Vaccination with live, killed, attenuated (physically or genetically) Leishmania have met with limited success, while peptide-, protein-, or DNA-based vaccines showed promise only in animal models. Here, we critically assess several technical issues in vaccination and expectation of a host-protective immune response. Several studies showed that antigen presentation during priming and triggering of the same cells in infected condition are not comparable. Altered proteolytic processing, antigen presentation, protease-susceptible sites, and intracellular expression of pathogenic proteins during Leishmania infection may vary dominant epitope selection, MHC-II/peptide affinity, and may deter the reactivation of desired antigen-specific T cells generated during priming. The robustness of the memory T cells and their functions remains a concern. Presentation of the antigens by Leishmania-infected macrophages to antigen-specific memory T cells may lead to change in the T cells’ functional phenotype or anergy or apoptosis. Although cells may be activated, the peptides generated during infection may be different and cross-reactive to the priming peptides. Such altered peptide ligands may lead to suppression of otherwise active antigen-specific T cells. We critically assess these different immunological issues that led to the non-availability of a vaccine for human use. Full article

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