Vaccines

10 pages, 844 KiB

Open AccessArticle

The COVID-19 mRNA BNT163b2 Vaccine Was Well Tolerated and Highly Immunogenic in Young Adults in Long Follow-Up after Haematopoietic Stem Cell Transplantation

by Agnieszka Matkowska-Kocjan, Joanna Owoc-Lempach, Joanna Chruszcz, Edwin Kuźnik, Filip Szenborn, Lidia Jurczenko, Marta Wójcik, Dorota Banyś, Leszek Szenborn and Marek Ussowicz

Vaccines 2021, 9(10), 1209; https://doi.org/10.3390/vaccines9101209 - 19 Oct 2021

Cited by 20 | Viewed by 3000

Abstract

Sixty five patients (18–31 years) who had received allogeneic haematopoietic stem cell transplantation (3–27 years from HSCT) were evaluated for the tolerance and immunogenicity of the COVID-19 mRNA BNT163b2 vaccine. Methods: Patients were vaccinated with two doses at 5 weeks interval. After each [...] Read more.

Sixty five patients (18–31 years) who had received allogeneic haematopoietic stem cell transplantation (3–27 years from HSCT) were evaluated for the tolerance and immunogenicity of the COVID-19 mRNA BNT163b2 vaccine. Methods: Patients were vaccinated with two doses at 5 weeks interval. After each dose, patients completed a survey concerning adverse events (AE) and anti-SARS-CoV-2 IgG antibodies were measured before the first vaccine dose (1stVD) and 14–21 days after the second dose (2ndVD). AE reported after 1stVD and 2ndVD, respectively were: fever 0%, 1.7%; fatigue 15.4%, 25.8%; headache 15.4%, 24.1%; chills 6.1%, 12.0%; muscle pain 15.4%, 24.1%; joint pain 3.0%, 6.9%; nausea 6.1%, 6.9%; pain at injection site 30.7%, 34.4%; swelling 3.0%, 10.3%; redness 0, 3.4%; pruritus 0, 5.2%; and axillary lymphadenopathy 3.0%, 1.7%. After 2ndVD, 96.5% patients were positive for anti-SARS-CoV-2 (GMC 3290.94 BAU/mL). No correlation presented between the antibody titer and symptoms of chronic Graft-versus-Host disease, total IgG, lymphocyte CD4+, or AE. Significantly higher titers were observed in COVID-19 convalescents, and inverse correlation (R² = −0.0925, p = 0.02) between the time from HSCT and titers after 2ndVD was present. Conclusions: The young adults after HSCT tolerate the COVID-19 mRNA vaccine well and show immunologic response. Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

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7 pages, 1314 KiB

Open AccessCommunication

Characterization of Individuals Interested in Participating in a Phase I SARS-CoV-2 Vaccine Trial

by Parichehr Shamsrizi, Frederik Johannes Kramer, Marylyn Martina Addo and Anahita Fathi

Vaccines 2021, 9(10), 1208; https://doi.org/10.3390/vaccines9101208 - 19 Oct 2021

Cited by 3 | Viewed by 2460

Abstract

The development of an effective vaccine against SARS-CoV-2 marks one of the highest priorities during the ongoing pandemic. However, recruitment of participants for clinical trials can be challenging, and recruitment failure is among the most common reasons for discontinuation in clinical trials. From [...] Read more.

The development of an effective vaccine against SARS-CoV-2 marks one of the highest priorities during the ongoing pandemic. However, recruitment of participants for clinical trials can be challenging, and recruitment failure is among the most common reasons for discontinuation in clinical trials. From 20 May 2020, public announcements about a planned phase I trial of the vaccine candidate MVA-SARS-2-S against SARS-CoV-2 began, and interested individuals started contacting the study team via designated e-mail. All emails received from these individuals between 20 May 2020–30 September 2020 were assessed. Of the 2541 interested volunteers, 62% contacted the study team within three days after the first media announcement. The average age was 61 years (range 16–100), 48% of volunteers were female and 52% male. A total of 274, 186, and 53 individuals, respectively, reported medical pre-conditions, were health-care workers, or had frequent inter-person contacts. In conclusion, we report a high number of volunteers, with a considerable percentage stating factors for an elevated risk to acquire COVID-19 or develop severe disease. Factors such as media coverage and the perception of a disease as an acute threat may influence the individual’s choice to volunteer for a vaccine trial. Our data provide first important insights to better understand reasons to participate in such trials to facilitate trial implementation and recruitment. Full article

(This article belongs to the Special Issue The COVID Vaccine)

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14 pages, 2909 KiB

Open AccessArticle

Associations between Allelic Variants of the Human IgH 3′ Regulatory Region 1 and the Immune Response to BNT162b2 mRNA Vaccine

by Mattia Colucci, Elisabetta De Santis, Beatrice Totti, Mattia Miroballo, Francesco Tamiro, Giovanni Rossi, Ada Piepoli, Gabriella De Vincentis, Antonio Greco, Alessandra Mangia, Rossella Cianci, Lazzaro Di Mauro, Giuseppe Miscio and Vincenzo Giambra

Vaccines 2021, 9(10), 1207; https://doi.org/10.3390/vaccines9101207 - 19 Oct 2021

Cited by 9 | Viewed by 2958

Abstract

The escalation of Coronavirus disease 2019 (COVID-19) has required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2), which is the causative agent of the disease. Here, we determined the levels of antibodies, antigen-specific B cells, [...] Read more.

The escalation of Coronavirus disease 2019 (COVID-19) has required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2), which is the causative agent of the disease. Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer–BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3’ regulatory region 1 (3’RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects. Taken together, these results suggest that favorable genetic backgrounds and immune profiles support the progression of an effective response to BNT162b2 vaccination. Full article

(This article belongs to the Special Issue Genomic Medicine and Advances in Vaccine Technology and Development 2.0)

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12 pages, 8859 KiB

Open AccessFeature PaperArticle

Vaccine Hesitancy and Trust in the Scientific Community in Italy: Comparative Analysis from Two Recent Surveys

by Chiara Cadeddu, Martina Sapienza, Carolina Castagna, Luca Regazzi, Andrea Paladini, Walter Ricciardi and Aldo Rosano

Vaccines 2021, 9(10), 1206; https://doi.org/10.3390/vaccines9101206 - 19 Oct 2021

Cited by 22 | Viewed by 4031

Abstract

Vaccination rates in Italy fell until 2015 because of unfounded safety concerns. Public education and a 2017 law on mandatory vaccination have boosted rates since then. The aim of our study is to explore how trust in the scientific community and attitudes towards [...] Read more.

Vaccination rates in Italy fell until 2015 because of unfounded safety concerns. Public education and a 2017 law on mandatory vaccination have boosted rates since then. The aim of our study is to explore how trust in the scientific community and attitudes towards vaccines have changed in the period of 2017–2019 in Italy. Data were extracted from the Italian section of the 2017 and 2019 editions of the European Social Survey (ESS). We compared the two surveys highlighting changes in public opinion on vaccines. A descriptive analysis of the socio-cultural variables according to the answers provided to key questions on the harmfulness of vaccines was conducted. Differences between percentages were tested by using the χ² test. The association between the opinion about the harmfulness of vaccines and trust in the scientific community was analyzed through a logistic regression model. Compared to ESS8, ESS9 showed an increase in the percentage of respondents disagreeing with the harmfulness of vaccines. Trust in the scientific community raised in the period from 2017 to 2019 (59% vs. 69.6%). Higher education was significantly associated with disagreement regarding the harmfulness of vaccines (odds ratio (OR) = 2.41; 95% confidence interval (95%CI) 1.75–3.31), the strongest predictor was trust in the scientific community (OR = 10.47; 95% CI 7.55–14.52). In Italy, trust in the scientific community and in vaccinations has grown significantly in recent years, indicating a paradigm shift in public opinion compared to the past. Central actions and effective public communication strategies might reduce vaccine hesitancy and could be essential to garner public trust. Full article

(This article belongs to the Collection Factors Associated with Vaccine Hesitancy)

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7 pages, 731 KiB

Open AccessArticle

Hepatitis E Virus Quasispecies in Cerebrospinal Fluid with Neurological Manifestations

by Florence Abravanel, Florence Nicot, Sébastien Lhomme, Michele Cazabat, Thomas Drumel, Aurélie Velay, Justine Latour, Julie Belliere, Pascal Cintas, Nassim Kamar and Jacques Izopet

Vaccines 2021, 9(10), 1205; https://doi.org/10.3390/vaccines9101205 - 19 Oct 2021

Cited by 10 | Viewed by 2003

Abstract

Hepatitis E virus (HEV) infection can lead to a variety of neurological disorders. While HEV RNA is known to be present in the central nervous system, HEV quasispecies in serum and cerebrospinal fluid (CSF) have rarely been explored. We studied the virus’ quasispecies [...] Read more.

Hepatitis E virus (HEV) infection can lead to a variety of neurological disorders. While HEV RNA is known to be present in the central nervous system, HEV quasispecies in serum and cerebrospinal fluid (CSF) have rarely been explored. We studied the virus’ quasispecies in the blood and the CSF of five patients at the onset of their neurological symptoms. The samples of three patients suffering from meningitis, neuralgic amyotrophy and acute inflammatory polyradiculoneuropathy were taken at the acute phase of the HEV infection. The samples from the other two patients were taken during the chronic phase (5 years after HEV diagnosis) when they presented with clinical signs of encephalitis. We sequenced at least 20 randomly polyproline regions of the selected virus clones. Phylogenetic analysis of the virus variants in the blood and the CSF revealed no virus compartmentalization for the three acute-phase patients but there was clear evidence of HEV quasispecies compartmentalization in the CSF of the two patients during chronic infection. In conclusion, prolonged infection in the immunocompromised condition can lead to independent virus replication in the liver and the tissues, producing viruses in CSF. Full article

(This article belongs to the Special Issue Hepatitis E Virus and Immunology Research)

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13 pages, 684 KiB

Open AccessArticle

The Impact of Social Media Exposure and Interpersonal Discussion on Intention of COVID-19 Vaccination among Nurses

by Meiqi Xin, Sitong Luo, Rui She, Xi Chen, Liping Li, Lijuan Li, Xiaojun Chen and Joseph T. F. Lau

Vaccines 2021, 9(10), 1204; https://doi.org/10.3390/vaccines9101204 - 19 Oct 2021

Cited by 20 | Viewed by 6557

Abstract

COVID-19 vaccine hesitancy among nurses is a global public health concern and it is imperative to understand associated factors. Information environment plays a critical role in shaping health behaviors, while few studies explored such effects in the context of COVID-19 vaccination. A cross-sectional [...] Read more.

COVID-19 vaccine hesitancy among nurses is a global public health concern and it is imperative to understand associated factors. Information environment plays a critical role in shaping health behaviors, while few studies explored such effects in the context of COVID-19 vaccination. A cross-sectional survey was conducted among 1902 nurses in China. The study investigated the effects of social media exposure/interpersonal discussion on intention of COVID-19 vaccination and tested whether perceived effectiveness of COVID-19 vaccines (perceived vaccine efficacy, perceived duration of protection, and perceived effectiveness in preventing resurgences) mediated such associations. Results showed that about 68.0% and 56.5% of the participants had an intention of free and self-paid COVID-19 vaccinations, respectively. Frequent social media exposure and interpersonal discussion were positively associated with vaccination intentions. Perceived vaccine efficacy significantly mediated the effects of frequent social media exposure and interpersonal discussion, whereas perceived effectiveness in preventing resurgences suppressed the effects of frequent social media exposure. In conclusion, the prevalence of intention of COVID-19 vaccination was relatively low among Chinese nurses and health promotion is needed. Frequent social media exposure and interpersonal discussion potentially enhanced vaccination intentions via increased perceived vaccine efficacy. The findings can help inform the development of relevant health communication interventions. Full article

(This article belongs to the Special Issue Emerging Issues Regarding COVID-19 Vaccination Behavior, Intention, and Resistance: Interdisciplinary Approaches)

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13 pages, 716 KiB

Open AccessArticle

Differences in Sources of Information, Risk Perception, and Cognitive Appraisals between People with Various Latent Classes of Motivation to Get Vaccinated against COVID-19 and Previous Seasonal Influenza Vaccination: Facebook Survey Study with Latent Profile Analysis in Taiwan

by Yi-Lung Chen, Yen-Ju Lin, Yu-Ping Chang, Wen-Jiun Chou and Cheng-Fang Yen

Vaccines 2021, 9(10), 1203; https://doi.org/10.3390/vaccines9101203 - 19 Oct 2021

Cited by 8 | Viewed by 3146

Abstract

The present study aimed (1) to identify distinct latent classes of motivation to get vaccinated against coronavirus disease 2019 (COVID-19) and previous seasonal influenza vaccination among people in Taiwan and (2) to examine the roles of sources of information, risk perception, and cognitive [...] Read more.

The present study aimed (1) to identify distinct latent classes of motivation to get vaccinated against coronavirus disease 2019 (COVID-19) and previous seasonal influenza vaccination among people in Taiwan and (2) to examine the roles of sources of information, risk perception, and cognitive appraisals of vaccination against COVID-19 in these classes. We recruited 1047 participants through a Facebook advertisement. The participants’ motivation to get vaccinated against COVID-19, previous seasonal influenza vaccination, sources of information about COVID-19 vaccination, risk perception of COVID-19, and cognitive appraisals of vaccination against COVID-19 were determined. We examined the participants’ motivation for COVID-19 vaccination and previous seasonal influenza vaccination through latent profile analysis. Four latent classes of motivation were identified: participants with high motivation for COVID-19 vaccination and high seasonal influenza vaccination, those with high motivation for COVID-19 vaccination but low seasonal influenza vaccination, those with low motivation for COVID-19 vaccination but high seasonal influenza vaccination, and those with low motivation for COVID-19 vaccination and low seasonal influenza vaccination. Compared with participants in the latent class of high motivation for COVID-19 vaccination and high seasonal influenza vaccination, those in the other three latent classes had lower levels of positive appraisals of COVID-19 vaccination; participants in the latent class of low motivation for COVID-19 vaccination and low seasonal influenza vaccination had lower risk perception of COVID-19 and were also less likely to obtain information about COVID-19 vaccination from the internet, friends, and family members. The various motivations and behaviors for vaccination, sources of information, risk perception, and cognitive appraisals of vaccination against COVID-19 should be considered in intervention programs aiming to increase people’s motivation to get vaccinated against COVID-19. Full article

(This article belongs to the Special Issue Vaccine Acceptance and Uptake: Insights from Behavioural and Social Sciences)

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14 pages, 649 KiB

Open AccessArticle

School-Level Variation in Coverage of Co-Administered dTpa and HPV Dose 1 in Three Australian States

by Cassandra Vujovich-Dunn, Susan Rachel Skinner, Julia Brotherton, Handan Wand, Jana Sisnowski, Rebecca Lorch, Mark Veitch, Vicky Sheppeard, Paul Effler, Heather Gidding, Alison Venn, Cristyn Davies, Jane Hocking, Lisa J. Whop, Julie Leask, Karen Canfell, Lena Sanci, Megan Smith, Melissa Kang, Meredith Temple-Smith, Michael Kidd, Sharyn Burns, Linda Selvey, Dennis Meijer, Sonya Ennis, Chloe A. Thomson, Nikole Lane, John Kaldor and Rebecca Guy Show full author list Hide full author list

Vaccines 2021, 9(10), 1202; https://doi.org/10.3390/vaccines9101202 - 19 Oct 2021

Cited by 6 | Viewed by 3666

Abstract

Background: Australian adolescents are routinely offered HPV and dTpa (diphtheria, tetanus, pertussis) vaccines simultaneously in the secondary school vaccination program. We identified schools where HPV initiation was lower than dTpa coverage and associated school-level factors across three states. Methods: HPV vaccination initiation rates [...] Read more.

Background: Australian adolescents are routinely offered HPV and dTpa (diphtheria, tetanus, pertussis) vaccines simultaneously in the secondary school vaccination program. We identified schools where HPV initiation was lower than dTpa coverage and associated school-level factors across three states. Methods: HPV vaccination initiation rates and dTpa vaccination coverage in 2016 were calculated using vaccine databases and school enrolment data. A multivariate analysis assessed sociodemographic and school-level factors associated with HPV initiation being >5% absolute lower than dTpa coverage. Results: Of 1280 schools included, the median school-level HPV initiation rate was 85% (interquartile range (IQR):75–90%) and the median dTpa coverage was 86% (IQR:75–92%). Nearly a quarter (24%) of all schools had HPV vaccination initiation >5% lower than dTpa coverage and 11 % had >10% difference. School-level factors independently associated with >5% difference were remote schools (aOR:3.5, 95% CI = 1.7–7.2) and schools in major cities (aOR:1.8, 95% CI = 1.0–3.0), small schools (aOR:3.3, 95% CI = 2.3–5.7), higher socioeconomic advantage (aOR:1.7, 95% CI = 1.1–2.6), and lower proportions of Language-background-other-than-English (aOR:1.9, 95% CI = 1.2–3.0). Conclusion: The results identified a quarter of schools had lower HPV than dTpa initiation coverage, which may indicate HPV vaccine hesitancy, and the difference was more likely in socioeconomically advantaged schools. As hesitancy is context specific, it is important to understand the potential drivers of hesitancy and future research needs to understand the reasons driving differential uptake. Full article

(This article belongs to the Special Issue Vaccination of Adolescents)

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6 pages, 217 KiB

Open AccessCase Report

Case Report: Marked Survival Advantage of Two Colorectal Cancer Patients with Liver Metastases Treated with Vigil and FOLFOX-6

by Vedin Barve, Ned Adams, Laura Stanbery, Luisa Manning, Staci Horvath, Gladice Wallraven, Ernest Bognar, Minal Barve and John Nemunaitis

Vaccines 2021, 9(10), 1201; https://doi.org/10.3390/vaccines9101201 - 18 Oct 2021

Cited by 5 | Viewed by 2127

Abstract

Colorectal cancer is the third most diagnosed cancer in the United States. Five-year survival rates remain low and many patients will develop liver metastasis. Vigil is an immunotherapy manufactured from autologous tumor cells and transfected ex vivo with a plasmid that encodes the [...] Read more.

Colorectal cancer is the third most diagnosed cancer in the United States. Five-year survival rates remain low and many patients will develop liver metastasis. Vigil is an immunotherapy manufactured from autologous tumor cells and transfected ex vivo with a plasmid that encodes the GM-CSF gene and bifunctional shRNA construct to knockdown furin. Here, we report two patients with colorectal cancer and resectable liver metastasis entered into a clinical trial involving Vigil in combination with standard of care modified FOLFOX-6 chemotherapy. The first dose of Vigil was given two weeks before the modified FOLFOX-6 regimen. Vigil treatment continued until Vigil supply was exhausted. Both patients exhibited remarkable response to combination therapy, demonstrating no evidence of disease recurrence for over eight years. Additionally, both patients demonstrated systemic immune response to Vigil therapy as tested by ELISPOT. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

9 pages, 259 KiB

Open AccessArticle

Attitudes toward the SARS-CoV-2 and Influenza Vaccination in the Metropolitan Cities of Bologna and Palermo, Italy

by Marco Montalti, Zeno Di Valerio, Flavia Rallo, Lorena Squillace, Claudio Costantino, Francesco Tomasello, Giulia Letizia Mauro, Michela Stillo, Paola Perrone, Davide Resi, Davide Gori, Francesco Vitale and Maria Pia Fantini

Vaccines 2021, 9(10), 1200; https://doi.org/10.3390/vaccines9101200 - 18 Oct 2021

Cited by 24 | Viewed by 2524

Abstract

Vaccine hesitancy (VH) is known to play a relevant role in thwarting the efforts toward reaching satisfactory influenza vaccination coverage, and has caused similar difficulties during the COVID-19 pandemic. This study aims to describe the phenomenon and produce insights on the reasons behind [...] Read more.

Vaccine hesitancy (VH) is known to play a relevant role in thwarting the efforts toward reaching satisfactory influenza vaccination coverage, and has caused similar difficulties during the COVID-19 pandemic. This study aims to describe the phenomenon and produce insights on the reasons behind VH. A survey was administered between December 2020 and February 2021 to adults living in the cities of Bologna and Palermo. Of the 443 subjects enrolled, 47.3% were likely to get the influenza vaccination, while 75.6% were willing to receive the COVID-19 vaccination. The most frequent determinants that motivated the willingness to get the COVID-19 vaccine were trust in the safety of vaccines and belief that the vaccine is an effective tool. As for people’s unwillingness to be vaccinated, being exposed to information that produced doubts about the vaccine and lack of trust in a newly developed vaccine were the most frequently involved determinants. Statistically significant positive associations were found between the willingness to be vaccinated and postgraduate education and the propensity towards influenza vaccination. A negative association with being over 40 years old and of female gender was also found. These results might have an impact in better understanding individual reasons behind VH, identifying which categories are more exposed to it and which strategies should be implemented. Full article

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

2 pages, 172 KiB

Open AccessEditorial

Importance of Education about Cervical Cancer and Its Preventive Measures for the Promotion of HPV Vaccine According to the WHO Strategies

by Yutaka Ueda and Etsuko Miyagi

Vaccines 2021, 9(10), 1199; https://doi.org/10.3390/vaccines9101199 - 18 Oct 2021

Cited by 4 | Viewed by 1923

Abstract

The World Health Organization (WHO) has officially declared a global strategy regarding the Elimination of Cervical Cancer in November 2020, which focuses on preventing cervical cancer through HPV vaccination, screening precancerous lesions and managing and treating invasive cervical cancer [...] Full article

(This article belongs to the Special Issue Latest National HPV Vaccine Programs and Outcomes in the World)

3 pages, 179 KiB

Open AccessEditorial

Fear of Influenza Resurgence amid COVID-19 Pandemic: Need for Effective Flu Vaccine Still Exists

by Danushka K. Wijesundara, Clare Williams, Wei Sun, Andrea Marias Furuya and Yoichi Furuya

Vaccines 2021, 9(10), 1198; https://doi.org/10.3390/vaccines9101198 - 18 Oct 2021

Cited by 3 | Viewed by 2200

Abstract

As influenza season was approaching in 2020, public health officials feared that influenza would worsen the COVID-19 situation [...] Full article

(This article belongs to the Special Issue Research in Immune Responses to Vaccines Antigen during Influenza A Infection)

12 pages, 1666 KiB

Open AccessArticle

Passive Immunisation against RHDV2 Induces Protection against Disease but Not Infection

by Robyn N. Hall, Tegan King, Tiffany W. O’Connor, Andrew J. Read, Sylvia Vrankovic, Melissa Piper and Tanja Strive

Vaccines 2021, 9(10), 1197; https://doi.org/10.3390/vaccines9101197 - 18 Oct 2021

Cited by 9 | Viewed by 2332

Abstract

Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to [...] Read more.

Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to manage wild rabbit populations, a major economic and environmental pest species. Releasing RHDV1 into populations with a high proportion of rabbits less than 8–10 weeks of age leads to non-lethal infection in many of these young animals, with subsequent seroconversion and long-term immunity against reinfection. In contrast, RHDV2 causes lethal disease even in young rabbits, potentially offering substantial benefits for rabbit management programs over RHDV1. However, it is not clear how acquired resistance from maternal antibodies may influence immunity after RHDV2 infection. In this study, we assessed serological responses after RHDV2 challenge in young rabbits of three different ages (5-, 7-, or 9-weeks-old) that were passively immunised with either high- (titre of 2560 by RHDV IgG ELISA; 2.41 mg/mL total protein) or low- (titre of 160–640 by RHDV IgG ELISA; 1.41 mg/mL total protein) dose RHDV2 IgG to simulate maternal antibodies. All rabbits treated with a high dose and 75% of those treated with a low dose of RHDV2 IgG survived virus challenge. Surviving animals developed robust lagovirus-specific IgA, IgM, and IgG responses within 10 days post infection. These findings demonstrate that the protection against RHDV2 conferred by passive immunisation is not sterilising. Correspondingly, this suggests that the presence of maternal antibodies in wild rabbit populations may impede the effectiveness of RHDV2 as a biocontrol. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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38 pages, 2211 KiB

Open AccessReview

COVID-19 Vaccine Platforms: Challenges and Safety Contemplations

by Hadeel T. Al-Jighefee, Hoda Najjar, Muna Nizar Ahmed, Abeer Qush, Sara Awwad and Layla Kamareddine

Vaccines 2021, 9(10), 1196; https://doi.org/10.3390/vaccines9101196 - 18 Oct 2021

Cited by 18 | Viewed by 13832

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic as of March 2020, creating a global crisis and claiming millions of lives. To halt the pandemic and alleviate its impact on society, economy, and public health, the development of vaccines [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic as of March 2020, creating a global crisis and claiming millions of lives. To halt the pandemic and alleviate its impact on society, economy, and public health, the development of vaccines and antiviral agents against SARS-CoV-2 was a dire need. To date, various platforms have been utilized for SARS-CoV-2 vaccine development, and over 200 vaccine candidates have been produced, many of which have obtained the United States Food and Drug Administration (FDA) approval for emergency use. Despite this successful development and licensure, concerns regarding the safety and efficacy of these vaccines have arisen, given the unprecedented speed of vaccine development and the newly emerging SARS-CoV-2 strains and variants. In this review, we summarize the different platforms used for Coronavirus Disease 2019 (COVID-19) vaccine development, discuss their strengths and limitations, and highlight the major safety concerns and potential risks associated with each vaccine type. Full article

(This article belongs to the Special Issue Vaccines and Vaccine Adjuvants/Immunomodulators for Infectious Diseases)

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35 pages, 12025 KiB

Open AccessReview

Emerging SARS-CoV-2 Variants: A Review of Its Mutations, Its Implications and Vaccine Efficacy

by Sindhu Ramesh, Manoj Govindarajulu, Rachel S. Parise, Logan Neel, Tharanath Shankar, Shriya Patel, Payton Lowery, Forrest Smith, Muralikrishnan Dhanasekaran and Timothy Moore

Vaccines 2021, 9(10), 1195; https://doi.org/10.3390/vaccines9101195 - 18 Oct 2021

Cited by 91 | Viewed by 7859

Abstract

The widespread increase in multiple severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants is causing a significant health concern in the United States and worldwide. These variants exhibit increased transmissibility, cause more severe disease, exhibit evasive immune properties, impair neutralization by antibodies from vaccinated [...] Read more.

The widespread increase in multiple severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants is causing a significant health concern in the United States and worldwide. These variants exhibit increased transmissibility, cause more severe disease, exhibit evasive immune properties, impair neutralization by antibodies from vaccinated individuals or convalescence sera, and reinfection. The Centers for Disease Control and Prevention (CDC) has classified SARS-CoV-2 variants into variants of interest, variants of concern, and variants of high consequence. Currently, four variants of concern (B.1.1.7, B.1.351, P.1, and B.1.617.2) and several variants of interests (B.1.526, B.1.525, and P.2) are characterized and are essential for close monitoring. In this review, we discuss the different SARS-CoV-2 variants, emphasizing variants of concern circulating the world and highlight the various mutations and how these mutations affect the characteristics of the virus. In addition, we discuss the most common vaccines and the various studies concerning the efficacy of these vaccines against different variants of concern. Full article

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12 pages, 404 KiB

Open AccessArticle

A Study of Hepatitis A Seroprevalence in a Paediatric and Adolescent Population of the Province of Florence (Italy) in the Period 2017–2018 Confirms Tuscany a Low Endemic Area

by Beatrice Zanella, Sara Boccalini, Massimiliano Alberto Biamonte, Duccio Giorgetti, Marco Menicacci, Benedetta Bonito, Alessandra Ninci, Emilia Tiscione, Francesco Puggelli, Giovanna Mereu, Working Group DHS, Working Group AOUMeyer, Working Group AUSLTC, Paolo Bonanni and Angela Bechini

Vaccines 2021, 9(10), 1194; https://doi.org/10.3390/vaccines9101194 - 17 Oct 2021

Cited by 3 | Viewed by 2428

Abstract

Background: Italy is considered an area with very low HAV (hepatitis A virus) endemicity. Currently in Italy the anti-HAV vaccine is recommended only for specific risk groups and there is no universal vaccination program. The aim of this study was to assess [...] Read more.

Background: Italy is considered an area with very low HAV (hepatitis A virus) endemicity. Currently in Italy the anti-HAV vaccine is recommended only for specific risk groups and there is no universal vaccination program. The aim of this study was to assess the level of immunity against hepatitis A in a sample of children and adolescents from the province of Florence. Methods: A total of 165 sera were collected from subjects aged 1 to 18 years, proportionally selected according to the general population size and stratified by age and sex. A qualitative evaluation of anti-HAV antibodies was performed using the enzyme-linked immunosorbent assay (ELISA). Anamnestic and vaccination status data were also collected. Results: Our study showed a hepatitis A seroprevalence of 9.1% in the enrolled population. A statistically significant difference in the prevalence of anti-HAV was found between Italian and non-Italian subjects. About half of the population having anti-HAV antibodies was reported to be vaccinated, and no cases of hepatitis A were found. Conclusions: The data from our study confirmed Tuscany as an area with low HAV endemicity and showed that hepatitis A seroprevalence is significantly higher in foreign children and adolescents. The presence of more seropositive subjects than those vaccinated was probably due to a natural immunization achieved through a subclinical infection and/or to underreporting of the surveillance systems. Full article

(This article belongs to the Special Issue Viral Hepatitis and Hepatocellular Carcinoma)

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7 pages, 213 KiB

Open AccessArticle

Genetic Insights into the Middle East Respiratory Syndrome Coronavirus Infection among Saudi People

by Hatem A. Abuelizz, Maha M. AlRasheed, Ali Alhoshani and Tariq Alhawassi

Vaccines 2021, 9(10), 1193; https://doi.org/10.3390/vaccines9101193 - 17 Oct 2021

Cited by 2 | Viewed by 2106

Abstract

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) was isolated for the first time in Saudi Arabia from a patient suffering from atypical pneumonia. The Saudi Genome database was built by King Abdulaziz Medical City via the next-generation sequencing of 7000 candidates. Method: [...] Read more.

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) was isolated for the first time in Saudi Arabia from a patient suffering from atypical pneumonia. The Saudi Genome database was built by King Abdulaziz Medical City via the next-generation sequencing of 7000 candidates. Method: A large list of point mutations were reported in the region of the dipeptidyl peptidase 4 (DPP4) gene. The DPP4 amino acid residues correlated to MERS-CoV entry and the site of activity of DPP4 inhibitors was investigated. We retrieved the SNPs (Single-Nucleotide Polymorphism) with a variation frequency of >0.05. Results: SNP 2:162,890,175 and SNP 2:162,891,848 in the intronic region were located within 50 bp of amino acid residues responsible for MERS-CoV entry, amino acids 259–296 and 205–258, respectively. The variation frequency of SNP 2:162,890,175 was 2321 out of 2379 screened individuals. Moreover, mutation of SNP 2:162,891,848, which is located near amino acid residues E205 and E206 (crucial for the activity of DPP4 inhibitors), occurred in 76 out of 2379 screened individuals. Conclusions: Our study shows high variation frequency in the DPP4 region reported in the Saudi Genome database. The identified SNPs are of high significance for MERS-CoV infection in better understanding disease pathogenesis. Full article

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

19 pages, 309 KiB

Open AccessArticle

Attitudes of Parents with Regard to Vaccination of Children against COVID-19 in Poland. A Nationwide Online Survey

by Mateusz Babicki, Dagmara Pokorna-Kałwak, Zbigniew Doniec and Agnieszka Mastalerz-Migas

Vaccines 2021, 9(10), 1192; https://doi.org/10.3390/vaccines9101192 - 17 Oct 2021

Cited by 44 | Viewed by 8347

Abstract

Within a few months, the scientific world achieved a great success, developing effective and safe vaccines against COVID-19. Many countries with full access to vaccines have introduced recommendations for the vaccination of not only people who are at risk of developing severe COVID-19, [...] Read more.

Within a few months, the scientific world achieved a great success, developing effective and safe vaccines against COVID-19. Many countries with full access to vaccines have introduced recommendations for the vaccination of not only people who are at risk of developing severe COVID-19, i.e., the elderly and chronically ill, but all members of society, including children aged 12 and above as the currently registered preparations can be used above the said age. However, the use of COVID-19 vaccines in children arouses strong emotions, with their sense being frequently questioned. The aim of the paper was to assess the attitudes of Polish parents with regard to vaccinations against COVID-19 administered to their children. The study was conducted with the use of the authors’ original questionnaire, which was distributed online. The questionnaire was completed 4732 times, and 4432 surveys were qualified for the final analysis. The vast majority of the respondents were women (77.6%), people aged 36–44 (40.3%), with higher education (86.2%) and people living in the city with more than 250,000 inhabitants (48%). The mean age of the study group was 37.5 ± 6.61 years. Out of the studied group, 28.2% of parents are healthcare professionals. The study was conducted prior to the EMA’s decision that permitted the use of BNT162b2 in children. Results: The vast majority of the respondents were mothers, who showed significantly more favorable attitudes toward the vaccinations than fathers. Forty-four percent of parents want to vaccinate their children as soon as possible, while every fourth parent does not want to vaccinate their child at all. Main concerns about the vaccines include concerns that the preparation has not been adequately tested and that it is ineffective, as well as the lack of information concerning potential complications in the future. The main sources of information on childhood vaccinations are the media, including the Internet and television. Vaccination of the pediatric population against COVID-19 raises many emotions and doubts in parents and it is also debated by experts. The decision to vaccinate should rest on child’s parents. Both the individual benefits of protection against COVID-19 and the population benefits of pandemic control must be considered. There is a need for ongoing monitoring of the safety of administering COVID-19 vaccinations in children, as well as for evaluating their effectiveness and benefits in reducing individual risk of severe course of COVID-19 and complications after this disease, and for evaluating the population benefits of vaccines in children. Full article

13 pages, 746 KiB

Open AccessArticle

Seroepidemiology of Measles, Mumps, Rubella and Varicella in Italian Female School Workers: A Cross-Sectional Study

by Nicola Frau, Federico Meloni, Jacopo Fostinelli, Laura Portas, Igor Portoghese, Emma Sala, Ilaria Pilia, Luigi Isaia Lecca, Giuseppe De Palma and Marcello Campagna

Vaccines 2021, 9(10), 1191; https://doi.org/10.3390/vaccines9101191 - 16 Oct 2021

Cited by 4 | Viewed by 2648

Abstract

Background: Determining the proportion of susceptible workers can represent a first step to the biological risk assessment related to measles, mumps, rubella and varicella exposure. This study aimed to assess the immunity against measles, mumps, rubella and varicella viruses in a cohort of [...] Read more.

Background: Determining the proportion of susceptible workers can represent a first step to the biological risk assessment related to measles, mumps, rubella and varicella exposure. This study aimed to assess the immunity against measles, mumps, rubella and varicella viruses in a cohort of female school workers. Methods: A cross-sectional seroepidemiological study in a sample of 263 school workers undergoing routine annual workplace health surveillance program was conducted. As part of the health surveillance program, serum samples were collected and tested for measles, mumps, rubella and varicella IgG antibodies. Results: Overall seropositivity was 90.5%, 85.2%, 94.7% and 97.3% for measles, mumps, rubella and varicella, respectively. In relation to mumps occupation-specific seropositivity, a statistically significant difference was observed, showing the lowest prevalence of protected individuals in other occupation groups. Moreover, in relation to rubella, school workers born in Centre Italy had the lowest seropositivity of protective antibodies and the difference between groups was statistically significant. Measles and rubella seropositivity showed a significant decrease after 2015. Conclusions: This study showed a relevant proportion of school workers susceptible to the aforementioned diseases. These results highlighted the need for proper health surveillance and immunological controls in school workers, especially for females, and provided useful insights to policymakers to select effective strategies aimed at containing the risk of vaccine-preventable diseases at schools. Full article

(This article belongs to the Section Epidemiology)

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17 pages, 4736 KiB

Open AccessArticle

Avian Cell Line DuckCelt^®-T17 Is an Efficient Production System for Live-Attenuated Human Metapneumovirus Vaccine Candidate Metavac^®

by Caroline Chupin, Andrés Pizzorno, Aurélien Traversier, Pauline Brun, Daniela Ogonczyk-Makowska, Blandine Padey, Cédrine Milesi, Victoria Dulière, Emilie Laurent, Thomas Julien, Marie Galloux, Bruno Lina, Jean-François Eléouët, Karen Moreau, Marie-Eve Hamelin, Olivier Terrier, Guy Boivin, Julia Dubois and Manuel Rosa-Calatrava

Vaccines 2021, 9(10), 1190; https://doi.org/10.3390/vaccines9101190 - 16 Oct 2021

Cited by 5 | Viewed by 3169

Abstract

The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with [...] Read more.

The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with traditional cell platforms used for viral vaccine manufacture. We investigated whether the DuckCelt^®-T17 avian cell line (Vaxxel), previously described as an efficient production system for several influenza strains, could also be used to produce a new HMPV LAV candidate (Metavac^®, SH gene-deleted A1/C-85473 HMPV). To that end, we characterized the operational parameters of MOI, cell density, and trypsin addition to achieve the optimal production of Metavac^®, and demonstrated that the DuckCelt^®-T17 cell line is permissive and well-adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac^® vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt^®-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, and its capacity to induce efficient neutralizing antibodies in a BALB/c mouse model. Our results suggest that the DuckCelt^®-T17 avian cell line is a very promising platform for the scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac^®. Full article

(This article belongs to the Collection Vaccines against Infectious Diseases)

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19 pages, 3570 KiB

Open AccessArticle

Novel Recombinant Newcastle Disease Virus-Based In Ovo Vaccines Bypass Maternal Immunity to Provide Full Protection from Early Virulent Challenge

by Kiril M. Dimitrov, Tonya L. Taylor, Valerie C. Marcano, Dawn Williams-Coplin, Timothy L. Olivier, Qingzhong Yu, Robert M. Gogal, Jr., David L. Suarez and Claudio L. Afonso

Vaccines 2021, 9(10), 1189; https://doi.org/10.3390/vaccines9101189 - 15 Oct 2021

Cited by 5 | Viewed by 3577

Abstract

Newcastle disease (ND) is one of the most economically important poultry diseases. Despite intensive efforts with current vaccination programs, this disease still occurs worldwide, causing significant mortality even in vaccinated flocks. This has been partially attributed to a gap in immunity during the [...] Read more.

Newcastle disease (ND) is one of the most economically important poultry diseases. Despite intensive efforts with current vaccination programs, this disease still occurs worldwide, causing significant mortality even in vaccinated flocks. This has been partially attributed to a gap in immunity during the post-hatch period due to the presence of maternal antibodies that negatively impact the replication of the commonly used live vaccines. In ovo vaccines have multiple advantages and present an opportunity to address this problem. Currently employed in ovo ND vaccines are recombinant herpesvirus of turkeys (HVT)-vectored vaccines expressing Newcastle disease virus (NDV) antigens. Although proven efficient, these vaccines have some limitations, such as delayed immunogenicity and the inability to administer a second HVT vaccine post-hatch. The use of live ND vaccines for in ovo vaccination is currently not applicable, as these are associated with high embryo mortality. In this study, recombinant NDV-vectored experimental vaccines containing an antisense sequence of avian interleukin 4 (IL4R) and their backbones were administered in ovo at different doses in 18-day-old commercial eggs possessing high maternal antibodies titers. The hatched birds were challenged with virulent NDV at 2 weeks-of-age. Post-hatch vaccine shedding, post-challenge survival, challenge virus shedding, and humoral immune responses were evaluated at multiple timepoints. Recombinant NDV (rNDV) vaccinated birds had significantly reduced post-hatch mortality compared with the wild-type LaSota vaccine. All rNDV vaccines were able to penetrate maternal immunity and induce a strong early humoral immune response. Further, the rNDV vaccines provided protection from clinical disease and significantly decreased virus shedding after early virulent NDV challenge at two weeks post-hatch. The post-challenge hemagglutination-inhibition antibody titers in the vaccinated groups remained comparable with the pre-challenge titers, suggesting the capacity of the studied vaccines to prevent efficient replication of the challenge virus. Post-hatch survival after vaccination with the rNDV-IL4R vaccines was dose-dependent, with an increase in survival as the dose decreased. This improved survival and the dose-dependency data suggest that novel attenuated in ovo rNDV-based vaccines that are able to penetrate maternal immunity to elicit a strong immune response as early as 14 days post-hatch, resulting in high or full protection from virulent challenge, show promise as a contributor to the control of Newcastle disease. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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12 pages, 1012 KiB

Open AccessArticle

Knowledge, Attitude, and Practice of Physicians Regarding Vaccinations in Yerevan, Armenia: A Case Study of HPV

by Arman R. Badalyan, Marine Hovhannisyan, Gayane Ghavalyan, Mary M. Ter-Stepanyan, Rory Cave, Jennifer Cole, Andrew W. K. Farlow and Hermine V. Mkrtchyan

Vaccines 2021, 9(10), 1188; https://doi.org/10.3390/vaccines9101188 - 15 Oct 2021

Cited by 4 | Viewed by 4623

Abstract

This paper highlights the low levels of vaccine coverage and high levels of reported vaccination hesitancy in Yerevan, Armenia, that present profound challenges to the control of disease through routine vaccination programmes. We draw on investigations of hesitancy towards the introduction of new [...] Read more.

This paper highlights the low levels of vaccine coverage and high levels of reported vaccination hesitancy in Yerevan, Armenia, that present profound challenges to the control of disease through routine vaccination programmes. We draw on investigations of hesitancy towards the introduction of new vaccines, using the Human Papillomavirus (HPV) vaccine Gardasil as a case study, to interrogate underlying challenges to vaccine acceptance. We analyse primary data from the introduction of Gardasil, first used in Armenia in 2017, to investigate how levels of medical knowledge amongst physicians in 20 health facilities in Yerevan, Armenia, regarding vaccine science influence attitudes towards the introduction of a newly developed vaccine. A questionnaire-based cross-sectional study was completed by 348 physicians between December 2017 and September 2018. The responding physicians displayed a respectable level of knowledge and awareness regarding vaccination with respect to some characteristics (e.g., more than 81% knew that HPV infection was commonly asymptomatic, 73% knew that HPV infection was implicated in most cervical cancers, and 87% knew that cervical cancer is the most prevalent cancer amongst women) but low knowledge and poor understanding of other key issues such as the age at which women were most likely to develop cervical cancer (only 15% answered correctly), whether or not the vaccine should be administered to people who had already been infected (27% answered correctly) and whether sexually active young people should be treated for infection before vaccination (26% answered correctly). The study suggests that the drivers of vaccine hesitancy are complex and may not be consistent from vaccine to vaccine. The Armenian healthcare sector may need to provide additional training, awareness-raising and educational activities alongside the introduction of new vaccines to improve understanding of and trust in vaccination programmes. Full article

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

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28 pages, 1806 KiB

Open AccessReview

Self-Replicating RNA Viruses for Vaccine Development against Infectious Diseases and Cancer

by Kenneth Lundstrom

Vaccines 2021, 9(10), 1187; https://doi.org/10.3390/vaccines9101187 - 15 Oct 2021

Cited by 34 | Viewed by 8367

Abstract

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered for recombinant protein expression and vaccine development. Due to the presence of RNA-dependent RNA polymerase activity, subgenomic RNA can replicate close to 10⁶ copies per cell for [...] Read more.

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered for recombinant protein expression and vaccine development. Due to the presence of RNA-dependent RNA polymerase activity, subgenomic RNA can replicate close to 10⁶ copies per cell for translation in the cytoplasm providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. Self-replicating RNA viral vectors can be administered as replicon RNA at significantly lower doses than conventional mRNA, recombinant particles, or DNA plasmids. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus, etc., showing robust immune response and protection in animal models. Recently, paramyxovirus and rhabdovirus vector-based SARS-CoV-2 vaccines as well as RNA vaccines based on self-amplifying alphaviruses have been evaluated in clinical settings. Vaccines against various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been developed. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use. Full article

(This article belongs to the Special Issue Vaccines against Infectious Diseases and Cancer)

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15 pages, 2559 KiB

Open AccessFeature PaperArticle

Shedding the Light on Post-Vaccine Myocarditis and Pericarditis in COVID-19 and Non-COVID-19 Vaccine Recipients

by Rima Hajjo, Dima A. Sabbah, Sanaa K. Bardaweel and Alexander Tropsha

Vaccines 2021, 9(10), 1186; https://doi.org/10.3390/vaccines9101186 - 15 Oct 2021

Cited by 65 | Viewed by 29503

Abstract

Myocarditis and pericarditis have been linked recently to COVID-19 vaccines without exploring the underlying mechanisms, or compared to cardiac adverse events post-non-COVID-19 vaccines. We introduce an informatics approach to study post-vaccine adverse events on the systems biology level to aid the prioritization of [...] Read more.

Myocarditis and pericarditis have been linked recently to COVID-19 vaccines without exploring the underlying mechanisms, or compared to cardiac adverse events post-non-COVID-19 vaccines. We introduce an informatics approach to study post-vaccine adverse events on the systems biology level to aid the prioritization of effective preventive measures and mechanism-based pharmacotherapy by integrating the analysis of adverse event reports from the Vaccine Adverse Event Reporting System (VAERS) with systems biology methods. Our results indicated that post-vaccine myocarditis and pericarditis were associated most frequently with mRNA COVID-19 vaccines followed by live or live-attenuated non-COVID-19 vaccines such as smallpox and anthrax vaccines. The frequencies of cardiac adverse events were affected by vaccine, vaccine type, vaccine dose, sex, and age of the vaccinated individuals. Systems biology results suggested a central role of interferon-gamma (INF-gamma) in the biological processes leading to cardiac adverse events, by impacting MAPK and JAK-STAT signaling pathways. We suggest that increasing the time interval between vaccine doses minimizes the risks of developing inflammatory adverse reactions. We also propose glucocorticoids as preferred treatments based on system biology evidence. Our informatics workflow provides an invaluable tool to study post-vaccine adverse events on the systems biology level to suggest effective mechanism-based pharmacotherapy and/or suitable preventive measures. Full article

(This article belongs to the Special Issue The COVID Vaccine)

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30 pages, 5740 KiB

Open AccessReview

From Bench to Field: A Guide to Formulating and Evaluating Anti-Tick Vaccines Delving beyond Efficacy to Effectiveness

by Charles Ndawula, Jr.

Vaccines 2021, 9(10), 1185; https://doi.org/10.3390/vaccines9101185 - 15 Oct 2021

Cited by 12 | Viewed by 4617

Abstract

Ticks are ubiquitous blood-sucking ectoparasites capable of transmitting a wide range of pathogens such as bacteria, viruses, protozoa, and fungi to animals and humans. Although the use of chemicals (acaricides) is the predominant method of tick-control, there are increasing incidents of acaricide tick [...] Read more.

Ticks are ubiquitous blood-sucking ectoparasites capable of transmitting a wide range of pathogens such as bacteria, viruses, protozoa, and fungi to animals and humans. Although the use of chemicals (acaricides) is the predominant method of tick-control, there are increasing incidents of acaricide tick resistance. Furthermore, there are concerns over accumulation of acaricide residues in meat, milk and in the environment. Therefore, alternative methods of tick-control have been proposed, of which anti-tick cattle vaccination is regarded as sustainable and user-friendly. Over the years, tremendous progress has been made in identifying and evaluating novel candidate tick vaccines, yet none of them have reached the global market. Until now, Bm86-based vaccines (Gavac™ in Cuba and TickGARD^PLUS™ Australia-ceased in 2010) are still the only globally commercialized anti-tick vaccines. In contrast to Bm86, often, the novel candidate anti-tick vaccines show a lower protection efficacy. Why is this so? In response, herein, the potential bottlenecks to formulating efficacious anti-tick vaccines are examined. Aside from Bm86, the effectiveness of other anti-tick vaccines is rarely assessed. So, how can the researchers assess anti-tick vaccine effectiveness before field application? The approaches that are currently used to determine anti-tick vaccine efficacy are re-examined in this review. In addition, a model is proposed to aid in assessing anti-tick vaccine effectiveness. Finally, based on the principles for the development of general veterinary vaccines, a pipeline is proposed to guide in the development of anti-tick vaccines. Full article

(This article belongs to the Special Issue Tick-Vaccine and Tick-Control)

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20 pages, 1028 KiB

Open AccessReview

The Immunology of Hepatocellular Carcinoma

by Gbemisola Lawal, Yao Xiao, Amir A. Rahnemai-Azar, Diamantis I. Tsilimigras, Ming Kuang, Anargyros Bakopoulos and Timothy M. Pawlik

Vaccines 2021, 9(10), 1184; https://doi.org/10.3390/vaccines9101184 - 15 Oct 2021

Cited by 41 | Viewed by 5450

Abstract

Liver cancer is the third leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Liver resection or transplantation offer the only potentially curative options for HCC; however, many patients are not candidates for [...] Read more.

Liver cancer is the third leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Liver resection or transplantation offer the only potentially curative options for HCC; however, many patients are not candidates for surgical resection, either due to presentation at advanced stages or poor liver function and portal hypertension. Liver transplantation is also limited to patients with certain characteristics, such as those that meet the Milan criteria (one tumor ≤ 5 cm, or up to three tumors no larger than 3 cm, along with the absence of gross vascular invasion or extrahepatic spread). Locoregional therapies, such as ablation (radiofrequency, ethanol, cryoablation, microwave), trans-arterial therapies like chemoembolization (TACE) or radioembolization (TARE), and external beam radiation therapy, have been used mainly as palliative measures with poor prognosis. Therefore, emerging novel systemic treatments, such as immunotherapy, have increasingly become popular. HCC is immunogenic, containing infiltrating tumor-specific T-cell lymphocytes and other immune cells. Immunotherapy may provide a more effective and discriminatory targeting of tumor cells through induction of a tumor-specific immune response in cancer cells and can improve post-surgical recurrence-free survival in HCC. We herein review evidence supporting different immunomodulating cell-based technology relative to cancer therapy in vaccines and targeted therapies, such as immune checkpoint inhibitors, in the management of hepatocellular carcinoma among patients with advanced disease. Full article

(This article belongs to the Special Issue The Immunology of Hepatocellular Carcinoma: Towards the Future of Immunotherapy)

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22 pages, 600 KiB

Open AccessFeature PaperArticle

Pharmaceutical Industry’s Engagement in the Global Equitable Distribution of COVID-19 Vaccines: Corporate Social Responsibility of EUL Vaccine Developers

by Meekang Sung, Yangmu Huang, Yuqi Duan, Fangjing Liu, Yinzi Jin and Zhijie Zheng

Vaccines 2021, 9(10), 1183; https://doi.org/10.3390/vaccines9101183 - 15 Oct 2021

Cited by 12 | Viewed by 6796

Abstract

(1) Objectives: Inequality in the global distribution of COVID-19 vaccines has brought about great challenges in terms of resolving the pandemic. Although vaccine manufacturers are undoubtedly some of the most influential players, studies on their role in global vaccine distribution have been scarce. [...] Read more.

(1) Objectives: Inequality in the global distribution of COVID-19 vaccines has brought about great challenges in terms of resolving the pandemic. Although vaccine manufacturers are undoubtedly some of the most influential players, studies on their role in global vaccine distribution have been scarce. This study examined whether the pharmaceutical industry is acting according to the principles of corporate social responsibility (CSR) during the pandemic. (2) Methods: Three categories were used to analyze the CSR of vaccine developers. The first was research and development: effectiveness, funding, and profits were measured. The second was transparency and accountability: the transparency of clinical trials and vaccine contracts was analyzed. The final was vaccine delivery: the status of the provision of vaccines to COVAX and lower-income countries, intellectual property management, manufacturing agreements, and equitable pricing were measured. (3) Results: Vaccine developers have acquired large profits. The vaccine delivery category faces the most challenges. Participation of pharmaceutical companies through COVAX was significantly low, and most vaccine supply agreements were secretive, bilateral deals. It was not clear if companies were maintaining equitable pricing. The evaluation indicated that the companies’ CSR practices have differed during the pandemic. (4) Conclusions: Our study contributes to the methodology of assessing the CSR of vaccine developers. This would help understand the current COVID-19 vaccine distribution inequality and propose that pharmaceutical companies re-examine their roles and social responsibilities. Full article

(This article belongs to the Special Issue COVID-19 Vaccination: Considerations for Public Health and Policy)

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17 pages, 3318 KiB

Open AccessArticle

Immune Response in Mice Immunized with Chimeric H1 Antigens

by Erasmus Nikoi Kotey, William Kwabena Ampofo, Rebecca Daines, Jean-Remy Sadeyen, Munir Iqbal and Osbourne Quaye

Vaccines 2021, 9(10), 1182; https://doi.org/10.3390/vaccines9101182 - 15 Oct 2021

Cited by 2 | Viewed by 2358

Abstract

Identification of a universal influenza vaccine candidate has remained a global challenge for both humans and animals. This study describes an approach that uses consensus sequence building to generate chimeric HAs (cHAs): two resultant H1 HA-based chimeras comprising of conserved sequences (within several [...] Read more.

Identification of a universal influenza vaccine candidate has remained a global challenge for both humans and animals. This study describes an approach that uses consensus sequence building to generate chimeric HAs (cHAs): two resultant H1 HA-based chimeras comprising of conserved sequences (within several areas spanning the head and stalk regions) of H1 and H5 or H9 HAs. These cHAs expressed in Drosophila cells (S2) were used to immunize mice. All immunized mice were protected from an infectious H1 virus challenge. Seroconverted mice sera to the H1 cHAs inhibited both the challenge virus and an H5 virus isolate by haemagglutination inhibition (HI) assay. These findings further emphasize that cHAs induce cross-reactive antibodies against conserved areas of both head and stalk regions of the seasonal influenza A (H1N1) pdm09 virus’ HA and holds potential for further development of a universal influenza vaccine. Full article

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13 pages, 1126 KiB

Open AccessArticle

A Data-Driven Digital Application to Enhance the Capacity Planning of the COVID-19 Vaccination Process

by Berend Markhorst, Tara Zver, Nina Malbasic, Renze Dijkstra, Daan Otto, Rob van der Mei and Dennis Moeke

Vaccines 2021, 9(10), 1181; https://doi.org/10.3390/vaccines9101181 - 15 Oct 2021

Cited by 7 | Viewed by 3528

Abstract

In this paper, a decision support system (DSS) is presented that focuses on the capacity planning of the COVID-19 vaccination process in the Netherlands. With the Dutch national vaccination priority list as the starting point, the DSS aims to minimize the per-class waiting-time [...] Read more.

In this paper, a decision support system (DSS) is presented that focuses on the capacity planning of the COVID-19 vaccination process in the Netherlands. With the Dutch national vaccination priority list as the starting point, the DSS aims to minimize the per-class waiting-time with respect to (1) the locations of the medical hubs (i.e., the vaccination locations) and (2) the distribution of the available vaccines and healthcare professionals (over time). As the user is given the freedom to experiment with different starting positions and strategies, the DSS is ideally suited for providing support in the dynamic environment of the COVID-19 vaccination process. In addition to the DSS, a mathematical model to support the assignment of inhabitants to medical hubs is presented. This model has been satisfactorily implemented in practice in close collaboration with the Dutch Municipal and Regional Health Service (GGD GHOR Nederland). Full article

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

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11 pages, 1409 KiB

Open AccessArticle

Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across All Ages: A Population-Based Modeling Study Using the UK as an Example

by Tinevimbo Shiri, Marc Evans, Carla A. Talarico, Angharad R. Morgan, Maaz Mussad, Philip O. Buck, Phil McEwan and William David Strain

Vaccines 2021, 9(10), 1180; https://doi.org/10.3390/vaccines9101180 - 15 Oct 2021

Cited by 17 | Viewed by 7019

Abstract

Debate persists around the risk–benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we [...] Read more.

Debate persists around the risk–benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we present a novel SEIR mathematical disease transmission model that quantifies the impact of different vaccination strategies on population-level SARS-CoV-2 infections and clinical outcomes. The model employs both age- and time-dependent social mixing patterns to capture the impact of changes in restrictions. The model was used to assess the impact of vaccinating adolescents and children on the natural history of the COVID-19 pandemic across all age groups, using the UK as an example. The base case model demonstrates significant increases in COVID-19 disease burden in the UK following a relaxation of restrictions, if vaccines are limited to those ≥18 years and vulnerable adolescents (≥12 years). Including adolescents and children in the vaccination program could reduce overall COVID-related mortality by 57%, and reduce cases of long COVID by 75%. This study demonstrates that vaccinating adolescents and children has the potential to play a vital role in reducing SARS-CoV-2 infections, and subsequent COVID-19 morbidity and mortality, across all ages. Our results have major global public health implications and provide valuable information to inform a potential pandemic exit strategy. Full article

(This article belongs to the Section Human Vaccines and Public Health)

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