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Vaccines
Volume 12
Issue 11
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Vaccines, Volume 12, Issue 11 (November 2024) – 98 articles

Cover Story (view full-size image): Pneumococcal disease in the elderly is an important Public Health question because of the potential burden of disease. In the Veneto Region, vaccination against pneumococcus is available on a voluntary basis. Through this study, we evaluated invasive pneumococcal disease in the elderly population of the Veneto Region and observed the epidemiological trends of circulating serotypes. The experience in our territory induces us to continue close surveillance along with typing of circulating serotypes in order to understand the evolutionary trajectories of the disease and refine preventive vaccine strategies. Our call is widespread surveillance, typing and vaccination. View this paper
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12 pages, 1880 KiB  
Systematic Review
Association Between Influenza Vaccine and Immune Thrombocytopenia: A Systematic Review and Meta-Analysis
by Zhicai Liu, Jing Wang, Zhaojun Lu, Yuyang Xu, Jian Du, Jiayin Han, Xuechao Zhang and Yan Liu
Vaccines 2024, 12(11), 1298; https://doi.org/10.3390/vaccines12111298 - 20 Nov 2024
Viewed by 277
Abstract
Background: Immune thrombocytopenia (ITP) is an uncommon but serious adverse reaction after vaccination. However, its association with vaccines other than the measles–mumps–rubella vaccine remains debatable. This study aimed to analyze ITP cases following influenza vaccination and assess any potential association. Methods: We performed [...] Read more.
Background: Immune thrombocytopenia (ITP) is an uncommon but serious adverse reaction after vaccination. However, its association with vaccines other than the measles–mumps–rubella vaccine remains debatable. This study aimed to analyze ITP cases following influenza vaccination and assess any potential association. Methods: We performed a systematic search of the Web of Science, Embase, and PubMed databases from their inception to 15 April 2024. Cases were characterized qualitatively, and relative risk was assessed using either fixed or random models. Results: A total of 24 studies were analyzed, including 16 patients from 14 case reports. Patients averaged 56.7 years old, half were female, and ten patients had a history of prior illness. The mean time between vaccination and diagnosis was 13.3 days. Treatment primarily involved corticosteroids or intravenous immunoglobulin, with most recovering within a month. The pooled odds ratio for ITP post-influenza vaccination was 0.94 (95%CI: 0.85–1.03). Subgroup analyses conducted according to the study design and vaccine type did not reveal any significant results. Conclusion: No evidence of an association between influenza vaccination and ITP was found. Further observational studies are required to verify this relationship. Full article
(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)
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14 pages, 2430 KiB  
Article
Preliminary Study on Type I Interferon as a Mucosal Adjuvant for Human Respiratory Syncytial Virus F Protein
by Hongqiao Hu, Li Zhang, Lei Cao, Jie Jiang, Yuqing Shi, Hong Guo, Yang Wang, Hai Li and Yan Zhang
Vaccines 2024, 12(11), 1297; https://doi.org/10.3390/vaccines12111297 - 20 Nov 2024
Viewed by 341
Abstract
Background: Human respiratory syncytial virus (HRSV) imposes a significant disease burden on infants and the elderly. Intranasal immunization using attenuated live vaccines and certain vector vaccines against HRSV has completed phase II clinical trials with good safety and efficacy.Recombinant protein vaccines for mucosal [...] Read more.
Background: Human respiratory syncytial virus (HRSV) imposes a significant disease burden on infants and the elderly. Intranasal immunization using attenuated live vaccines and certain vector vaccines against HRSV has completed phase II clinical trials with good safety and efficacy.Recombinant protein vaccines for mucosal immunization require potent mucosal adjuvants. Type I interferon (IFN), as a natural mucosal adjuvant, significantly enhances antigen-presenting cell processing and antigen presentation, promoting the production of T and B cells. Methods: This study utilized human α2b interferon (IFN-human) and mouse α2 interferon (IFN-mouse) as nasal mucosal adjuvants in combination with fusion protein (F). Intranasal immunization was performed on BALB/c mice to evaluate the immunogenicity of the formulation in vivo. Results: Compared to the F protein immunization group, mice in the F + IFN-Human and F + IFN-Mouse experimental groups exhibited significantly increased neutralizing antibody titers and augmented secretion of IFN-γ and IL-4 by lymphocytes,  and both of them could induce the production of high-titer specific IgA antibodies in mice (p < 0.001).The F + IFN-Human immunization induced the highest IgG and IgG1 antibody titers in mice; however, the F + IFN-Mouse immunization group elicited the highest neutralizing antibody titers (598), lowest viral loads in the lungs (Ct value of 31), and fastest weight recovery in mice. Moreover, mice in the F + IFN-Mouse immunization group displayed the mildest lung pathological damage (Total score of pathological injury was 2). Conclusions: In conclusion, IFN-Mouse, as a mucosal adjuvant for HRSV recombinant protein vaccines, demonstrated superior protective effects in mice compared to IFN-Human adjuvants. Full article
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14 pages, 10252 KiB  
Review
Childhood Mandatory Vaccinations: Current Situation in European Countries and Changes Occurred from 2014 to 2024
by Sara Farina, Alessandra Maio, Maria Rosaria Gualano, Walter Ricciardi and Leonardo Villani
Vaccines 2024, 12(11), 1296; https://doi.org/10.3390/vaccines12111296 - 20 Nov 2024
Viewed by 361
Abstract
Background/Objectives: Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) [...] Read more.
Background/Objectives: Vaccination is one of the most effective public health interventions, preventing millions of deaths globally each year. However, vaccine hesitancy, driven by misinformation and reduced disease risk perception, has led to declining vaccination rates and the resurgence of vaccine-preventable diseases (VPDs) in Europe. In response to this, countries have implemented various strategies, including mandatory and recommended vaccination programs. The objective of this study is to map the current European landscape of pediatric vaccination policies, and the variations that have occurred in the last decade. Methods: This rapid review was conducted on PubMed, Google, and the European Centre for Disease Prevention and Control website, to collect all vaccination schedules in EU/EEA countries in 2024 and all documents focusing on the introduction of mandatory vaccines during the last decade. Results: As of 2024, 13 countries had at least one mandatory pediatric vaccination, with France, Hungary, and Latvia requiring all but one vaccine. In contrast, 17 countries had no mandatory vaccinations, relying only on recommendations. Between 2014 and 2024, six countries (Croatia, France, Germany, Hungary, Italy, and Poland) introduced or extended mandatory vaccinations. Conclusions: European vaccination policies show significant variation. Effective programs depend on robust healthcare systems, public trust, and adaptable strategies to address vaccine hesitancy and the resurgence of VPDs. Full article
(This article belongs to the Special Issue Advance Public Health through Vaccination)
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14 pages, 1260 KiB  
Article
Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021–May 2023
by Camelia Savulescu, Albert Prats-Uribe, Kim Brolin, Zvjezdana Lovrić Makarić, Anneli Uusküla, Georgios Panagiotakopoulos, Colm Bergin, Catherine Fleming, Antonella Agodi, Paolo Bonfanti, Rita Murri, Viesturs Zvirbulis, Dace Zavadska, Konstanty Szuldrzynski, Ausenda Machado, Corneliu Petru Popescu, Mihai Craiu, Maria Cisneros, Miriam Latorre-Millán, Goranka Petrović, Liis Lohur, Kyriaki Tryfinopoulou, Jonathan McGrath, Lauren Ferguson, Martina Barchitta, Anna Spolti, Katleen de Gaetano Donati, Ilze Abolina, Dagne Gravele, Vânia Gaio, Simin Aysel Florescu, Mihaela Lazar, Pilar Subirats, Laura Clusa Cuesta, Gordan Sarajlić, Marina Amerali, Jacklyn Sui, Claire Kenny, Venerando Rapisarda, Marianna Rossi, Silvia Lamonica, Dainis Krievins, Elza Anna Barzdina, Ana Palmira Amaral, Alma Gabriela Kosa, Victor Daniel Miron, Carmen Muñoz-Almagro, Ana María Milagro, Sabrina Bacci, Piotr Kramarz, Anthony Nardone and the VEBIS HCW VE Study Groupadd Show full author list remove Hide full author list
Vaccines 2024, 12(11), 1295; https://doi.org/10.3390/vaccines12111295 - 19 Nov 2024
Viewed by 479
Abstract
Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 [...] Read more.
Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May–6 September 2021), Delta (7 September–14 December 2021), and Omicron (15 December 2021–2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: −25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7–90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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16 pages, 2872 KiB  
Protocol
Multiparameter Flow Cytometric Analysis of the Conventional and Monocyte-Derived DC Compartment in the Murine Spleen
by Ronald A. Backer, Hans Christian Probst and Björn E. Clausen
Vaccines 2024, 12(11), 1294; https://doi.org/10.3390/vaccines12111294 - 19 Nov 2024
Viewed by 280
Abstract
Dendritic cells (DCs) are present in almost all tissues, where they act as sentinels involved in innate recognition and the initiation of adaptive immune responses. The DC family consists of several cell lineages that are heterogenous in their development, phenotype, and function. Within [...] Read more.
Dendritic cells (DCs) are present in almost all tissues, where they act as sentinels involved in innate recognition and the initiation of adaptive immune responses. The DC family consists of several cell lineages that are heterogenous in their development, phenotype, and function. Within these DC lineages, further subdivisions exist, resulting in smaller, less characterized subpopulations, each with its unique immunomodulatory capabilities. Given the interest in utilizing DC for experimental studies and for vaccination purposes, it becomes increasingly crucial to thoroughly classify and characterize these diverse DC subpopulations. This understanding is vital for comprehending their relative contribution to the initiation, regulation, and propagation of immune responses. To facilitate such investigation, we here provide an easy and ready-to-use multicolor flow cytometry staining panel for the analysis of conventional DC, plasmacytoid DC, and monocyte-derived DC populations isolated from mouse spleens. This adaptable panel can be easily customized for the analysis of other tissue-specific DC populations, providing a valuable tool for DC research. Full article
(This article belongs to the Special Issue Dendritic Cells (DCs) and Cancer Immunotherapy)
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14 pages, 681 KiB  
Review
Human Papillomavirus (HPV) Vaccination: Progress, Challenges, and Future Directions in Global Immunization Strategies
by Francesco Branda, Grazia Pavia, Alessandra Ciccozzi, Angela Quirino, Nadia Marascio, Simona Gigliotti, Giovanni Matera, Chiara Romano, Chiara Locci, Ilenia Azzena, Noemi Pascale, Daria Sanna, Marco Casu, Giancarlo Ceccarelli, Massimo Ciccozzi and Fabio Scarpa
Vaccines 2024, 12(11), 1293; https://doi.org/10.3390/vaccines12111293 - 19 Nov 2024
Viewed by 520
Abstract
Human papillomavirus (HPV) is a widespread viral pathogen, responsible for a significant burden of cervical and other cancers worldwide. Over the past decades, the development and widespread adoption of prophylactic HPV vaccines have dramatically reduced the incidence of HPV-related diseases. However, despite the [...] Read more.
Human papillomavirus (HPV) is a widespread viral pathogen, responsible for a significant burden of cervical and other cancers worldwide. Over the past decades, the development and widespread adoption of prophylactic HPV vaccines have dramatically reduced the incidence of HPV-related diseases. However, despite the efficacy of these vaccines, global immunization efforts still face several obstacles, including low vaccination coverage in low- and middle-income countries, vaccine hesitancy, and disparities in access to healthcare. This review aims to provide a comprehensive overview of the current state of HPV vaccines, including their mechanisms of action, safety profiles, and real-world efficacy. We will explore the impact of HPV vaccines on cancer prevention, examine the challenges related to vaccine distribution and uptake, and assess the role of public health policies in improving global vaccination rates. Additionally, the review will highlight the latest advancements in therapeutic HPV vaccines, ongoing research into next-generation vaccines, and the potential of HPV vaccination strategies in the context of personalized medicine. By examining these factors, we aim to provide insights into the future directions of HPV vaccination and its role in global public health. Full article
(This article belongs to the Special Issue Vaccines and Vaccination: HIV, Hepatitis Viruses, and HPV)
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19 pages, 3264 KiB  
Article
Sindbis Virus Replicon-Based SARS-CoV-2 and Dengue Combined Vaccine Candidates Elicit Immune Responses and Provide Protective Immunity in Mice
by Yihan Zhu, Wenfeng He, Rui Hu, Xiahua Liu, Mengzhu Li and Yuan Liu
Vaccines 2024, 12(11), 1292; https://doi.org/10.3390/vaccines12111292 - 19 Nov 2024
Viewed by 465
Abstract
Background/Objectives: Since its emergence in 2019, the rapid spread of SARS-CoV-2 led to the global pandemic. Recent large-scale dengue fever outbreaks overlapped with the COVID-19 pandemic, leading to increased cases of co-infection and posing severe public health risks. Accordingly, the development of [...] Read more.
Background/Objectives: Since its emergence in 2019, the rapid spread of SARS-CoV-2 led to the global pandemic. Recent large-scale dengue fever outbreaks overlapped with the COVID-19 pandemic, leading to increased cases of co-infection and posing severe public health risks. Accordingly, the development of effective combined SARS-CoV-2 and dengue virus (DENV) vaccines is necessary to control the spread and prevalence of both viruses. Methods: In this study, we designed Sindbis virus (SINV) replicon-based SARS-CoV-2 and DENV chimeric vaccines using two delivery strategies: DNA-launched self-replicating RNA replicon (DREP) and viral replicon particle (VRP) systems. Results: Cellular and animal experiments confirmed that the vaccines effectively produced viral proteins and elicited strong immunogenicity. These vaccines induced robust immune responses and neutralizing activity against live SARS-CoV-2, DENV1, and DENV2 viruses. In addition, passively transferred sera from BALB/c mice immunized with these vaccines into AG129 mice provided significant protection against lethal DENV2 challenge. The transferred sera protected the mice from physical symptoms, reduced viral loads in the kidney, spleen, liver, and intestine, and prevented DENV2-induced vascular leakage in these tissues. Conclusions: Therefore, combined vaccines based on the SINV replicon system are promising candidates for pandemic control. These results lay a foundation for further development of a safe and effective combination vaccine against SARS-CoV-2 and DENV. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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22 pages, 359 KiB  
Review
Human Papillomavirus-Related Cancer Vaccine Strategies
by Xia Cai and Ling Xu
Vaccines 2024, 12(11), 1291; https://doi.org/10.3390/vaccines12111291 - 19 Nov 2024
Viewed by 569
Abstract
Background: Human papillomavirus (HPV) persistent infection is a major pathogenic factor for HPV-related cancers, such as cervical cancer (CC), vaginal cancer, vulvar cancer, anal cancer, penile cancer, and head and neck cancer (HNC). Since the introduction of the world’s first prophylactic HPV vaccine, [...] Read more.
Background: Human papillomavirus (HPV) persistent infection is a major pathogenic factor for HPV-related cancers, such as cervical cancer (CC), vaginal cancer, vulvar cancer, anal cancer, penile cancer, and head and neck cancer (HNC). Since the introduction of the world’s first prophylactic HPV vaccine, there has been a decline in the incidence of HPV infections and associated cancers. This article reviews the latest literature on the research progress, efficacy, and safety of HPV vaccines for these cancers, providing a reference for HPV vaccination strategy. Methods: By utilizing databases such as PubMed, Google Scholar, CNKI, and Wanfang, we conducted a literature search on research papers related to HPV vaccines from 2014 to 2024, employing keywords such as “HPV”, “HPV vaccine”, “CC”, ”vaginal cancer”, “vulvar cancer”, “anal cancer”, “penile cancer” and “HNC”. Additionally, we reviewed the latest information available on official websites, including the World Health Organization (WHO). Based on the quality and relevance of the papers, we selected over 100 of the most representative articles for further summarization and analysis. Results: Vaccination against HPV can effectively block the transmission of the virus and prevent HPV-related cancers. Current studies have confirmed the efficacy and safety of prophylactic HPV vaccination. However, numerous challenges remain. The global vaccination rate for preventive vaccines remains low, particularly in low- and middle-income countries. Nonetheless, in the future, we can enhance the accessibility, affordability, and coverage of HPV vaccines by expanding the indications of already licensed vaccines, continuously developing new vaccines. Conclusions: The HPV vaccine is an extremely effective measure for the prevention and treatment of HPV-related cancers. Although there are many challenges in expanding the coverage of the HPV vaccine. It is believed that in the not-too-distant future, both prophylactic and therapeutic HPV vaccines will achieve commendable results. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers)
20 pages, 1890 KiB  
Review
Nanoparticles as Delivery Systems for Antigenic Saccharides: From Conjugation Chemistry to Vaccine Design
by Marie-Jeanne Archambault, Laetitia Mwadi Tshibwabwa, Mélanie Côté-Cyr, Serge Moffet, Tze Chieh Shiao and Steve Bourgault
Vaccines 2024, 12(11), 1290; https://doi.org/10.3390/vaccines12111290 - 19 Nov 2024
Viewed by 676
Abstract
Glycoconjugate vaccines have been effective in preventing numerous bacterial infectious diseases and have shown recent potential to treat cancers through active immunotherapy. Soluble polysaccharides elicit short-lasting immune responses and are usually covalently linked to immunogenic carrier proteins to enhance the antigen-specific immune response [...] Read more.
Glycoconjugate vaccines have been effective in preventing numerous bacterial infectious diseases and have shown recent potential to treat cancers through active immunotherapy. Soluble polysaccharides elicit short-lasting immune responses and are usually covalently linked to immunogenic carrier proteins to enhance the antigen-specific immune response by stimulating T-cell-dependent mechanisms. Nonetheless, the conjugation of purified polysaccharides to carrier proteins complexifies vaccine production, and immunization with protein glycoconjugates can lead to the undesirable immunogenic interference of the carrier. Recently, the use of nanoparticles and nanoassemblies for the delivery of antigenic saccharides has gathered attention from the scientific community. Nanoparticles can be easily functionalized with a diversity of functionalities, including T-cell epitope, immunomodulator and synthetic saccharides, allowing for the modulation and polarization of the glycoantigen-specific immune response. Notably, the conjugation of glycan to nanoparticles protects the antigens from degradation and enhances their uptake by immune cells. Different types of nanoparticles, such as liposomes assembled from lipids, inorganic nanoparticles, virus-like particles and dendrimers, have been explored for glycovaccine design. The versatility of nanoparticles and their ability to induce robust immune responses make them attractive delivery platforms for antigenic saccharides. The present review aims at summarizing recent advancements in the use of nano-scaled systems for the delivery of synthetic glycoantigens. After briefly presenting the immunological mechanisms required to promote a robust immune response against antigenic saccharides, this review will offer an overview of the current trends in the nanoparticle-based delivery of glycoantigens. Full article
(This article belongs to the Special Issue Advances in Glycoconjugate Vaccines and Nanovaccines)
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19 pages, 340 KiB  
Review
Impact of Immunosenescence on Vaccine Immune Responses and Countermeasures
by Li Chen, Chengwei Shao, Jingxin Li and Fengcai Zhu
Vaccines 2024, 12(11), 1289; https://doi.org/10.3390/vaccines12111289 - 19 Nov 2024
Viewed by 387
Abstract
The biological progression of aging encompasses complex physiological processes. As individuals grow older, their physiological functions gradually decline, including compromised immune responses, leading to immunosenescence. Immunosenescence significantly elevates disease susceptibility and severity in older populations while concurrently compromising vaccine-induced immune responses. This comprehensive [...] Read more.
The biological progression of aging encompasses complex physiological processes. As individuals grow older, their physiological functions gradually decline, including compromised immune responses, leading to immunosenescence. Immunosenescence significantly elevates disease susceptibility and severity in older populations while concurrently compromising vaccine-induced immune responses. This comprehensive review aims to elucidate the implications of immunosenescence for vaccine-induced immunity and facilitate the development of optimized vaccination strategies for geriatric populations, with specific focus on COVID-19, influenza, pneumococcal, herpes zoster, and respiratory syncytial virus (RSV) vaccines. This review further elucidates the relationship between immunosenescence and vaccine-induced immunity. This review presents a systematic evaluation of intervention strategies designed to enhance vaccine responses in older populations, encompassing adjuvant utilization, antigen doses, vaccination frequency modification, inflammatory response modulation, and lifestyle interventions, including physical activity and nutritional modifications. These strategies are explored for their potential to improve current vaccine efficacy and inform the development of next-generation vaccines for geriatric populations. Full article
25 pages, 4063 KiB  
Article
First-in-Human Phase I Trial to Assess the Safety and Immunogenicity of an Orf Virus-Based COVID-19 Vaccine Booster
by Meral Esen, Johanna Fischer-Herr, Julian Justin Gabor, Johanna Marika Gaile, Wim Alexander Fleischmann, Geerten Willem Smeenk, Roberta Allgayer de Moraes, Sabine Bélard, Carlos Lamsfus Calle, Tamirat Gebru Woldearegai, Diane Egger-Adam, Verena Haug, Carina Metz, Alena Reguzova, Markus W. Löffler, Baiba Balode, Lars C. Matthies, Michael Ramharter, Ralf Amann and Peter G. Kremsner
Vaccines 2024, 12(11), 1288; https://doi.org/10.3390/vaccines12111288 - 18 Nov 2024
Viewed by 526
Abstract
The emergence of SARS-CoV-2 has necessitated the development of versatile vaccines capable of addressing evolving variants. Prime-2-CoV_Beta, a novel Orf virus-based COVID-19 vaccine, was developed to express the SARS-CoV-2 spike and nucleocapsid antigens. This first-in-human, phase I, dose-finding clinical trial was conducted to [...] Read more.
The emergence of SARS-CoV-2 has necessitated the development of versatile vaccines capable of addressing evolving variants. Prime-2-CoV_Beta, a novel Orf virus-based COVID-19 vaccine, was developed to express the SARS-CoV-2 spike and nucleocapsid antigens. This first-in-human, phase I, dose-finding clinical trial was conducted to assess the safety, reactogenicity, and immunogenicity of Prime-2-CoV_Beta as a booster in healthy adults. From June 2022 to June 2023, 60 participants in Germany received varying doses of Prime-2-CoV_Beta. The study demonstrated a favorable safety profile, with no serious adverse events (AEs) reported. All AEs were mild (107) or moderate (10), with the most common symptoms being pain at the injection site, fatigue, and headache. Immunogenicity assessments revealed robust vaccine-induced antigen-specific immune responses. High doses notably elicited significant increases in antibodies against the spike and nucleocapsid proteins as well as neutralizing antibodies against SARS-CoV-2 and its variants. Additionally, the vaccine did not induce ORFV-neutralizing antibodies, indicating the potential for repeated administration. In conclusion, Prime-2-CoV_Beta was safe, well tolerated, and immunogenic, demonstrating potential as a broadly protective vaccine against SARS-CoV-2 and its variants. These promising results support further evaluation of higher doses and additional studies to confirm efficacy and long-term protection. This trial was registered at ClinicalTrials, NCT05389319. Full article
(This article belongs to the Special Issue Research in Innate and Adaptive Immunity)
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20 pages, 2059 KiB  
Review
Engineering Escherichia coli-Derived Nanoparticles for Vaccine Development
by Shubing Tang, Chen Zhao and Xianchao Zhu
Vaccines 2024, 12(11), 1287; https://doi.org/10.3390/vaccines12111287 - 18 Nov 2024
Viewed by 718
Abstract
The development of effective vaccines necessitates a delicate balance between maximizing immunogenicity and minimizing safety concerns. Subunit vaccines, while generally considered safe, often fail to elicit robust and durable immune responses. Nanotechnology presents a promising approach to address this dilemma, enabling subunit antigens [...] Read more.
The development of effective vaccines necessitates a delicate balance between maximizing immunogenicity and minimizing safety concerns. Subunit vaccines, while generally considered safe, often fail to elicit robust and durable immune responses. Nanotechnology presents a promising approach to address this dilemma, enabling subunit antigens to mimic critical aspects of native pathogens, such as nanoscale dimensions, geometry, and highly repetitive antigen display. Various expression systems, including Escherichia coli (E. coli), yeast, baculovirus/insect cells, and Chinese hamster ovary (CHO) cells, have been explored for the production of nanoparticle vaccines. Among these, E. coli stands out due to its cost-effectiveness, scalability, rapid production cycle, and high yields. However, the E. coli manufacturing platform faces challenges related to its unfavorable redox environment for disulfide bond formation, lack of post-translational modifications, and difficulties in achieving proper protein folding. This review focuses on molecular and protein engineering strategies to enhance protein solubility in E. coli and facilitate the in vitro reassembly of virus-like particles (VLPs). We also discuss approaches for antigen display on nanocarrier surfaces and methods to stabilize these carriers. These bioengineering approaches, in combination with advanced nanocarrier design, hold significant potential for developing highly effective and affordable E. coli-derived nanovaccines, paving the way for improved protection against a wide range of infectious diseases. Full article
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13 pages, 1687 KiB  
Article
A Comprehensive Evaluation of the HPV Neutralizing Antibodies in Guangzhou, China: A Comparative Study on Various HPV Vaccines
by Renyun Zha, Conghui Liao, Daner Lin, Lixuan Zhao, Yanfang Chen, Lin Yao, Xiaokang Li, Boyang Yi, Ting Li, Jianpeng Xiao, Yan Hu, Zeliang Chen, Cheng Guo, Jianyun Lu and Jiahai Lu
Vaccines 2024, 12(11), 1286; https://doi.org/10.3390/vaccines12111286 - 17 Nov 2024
Viewed by 484
Abstract
Background: The evaluation of HPV vaccine effectiveness is essential for informing public health strategies, yet there remains a gap in understanding humoral immune responses generated by different HPV vaccine formulations in regional populations. This study addresses this gap by evaluating the immunogenicity of [...] Read more.
Background: The evaluation of HPV vaccine effectiveness is essential for informing public health strategies, yet there remains a gap in understanding humoral immune responses generated by different HPV vaccine formulations in regional populations. This study addresses this gap by evaluating the immunogenicity of the newly developed HPV vaccine Cecolin (Wantai), alongside various imported vaccines, including bivalent, quadrivalent, and nonavalent options available in China. Methods: From March 2023 to June 2024, a total of 352 participants were enrolled, including 87 females aged 9–14 years who received two doses of the bivalent HPV vaccine (Cecolin), 215 females aged 15–45 years who were fully vaccinated with various HPV vaccines, and 50 non-recipients. Follow-up assessments were conducted at six timepoints during the administration of Cecolin. Serum was collected at enrollment and at each follow-up visit for antibody assessments using a pseudovirion-based neutralization assay (PBNA). Findings: The longitudinal follow-up of females aged 9–14 years revealed a 100% conversion rate for neutralizing antibodies against HPV types 16 and 18 after the second dose, compared to 94.3% and 97.1% conversion rates six months after the first dose. Compared to participants who received full doses of quadrivalent and nonavalent vaccines, females who received two or three doses of Cecolin exhibited higher neutralizing antibody geometric mean titers (GMTs) and non-vaccine-type (HPV31 and HPV33) antibody seroconversion rates. Interpretation: The domestically produced HPV vaccine Cecolin in China demonstrates strong immunogenicity and holds promise for the large-scale vaccination of females in developing countries to prevent cervical cancer. Full article
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17 pages, 5114 KiB  
Article
Newcastle Disease Virus Expressing Cap Gene of Porcine Circovirus Type 2 Confers Protection in Mice and Induced Long-Lasting Neutralizing Antibodies in Pigs
by Sohini Dey, Rudhreswaran Murugasamy, Lukumoni Buragohain, Ajai Lawrence D’silva, Jayashree Sarma, Arpita Bharali, Saravanan Ramakrishnan, Mani Saminathan, Nagendra Nath Barman, Vikram N. Vakharia and Madhan Mohan Chellappa
Vaccines 2024, 12(11), 1285; https://doi.org/10.3390/vaccines12111285 - 15 Nov 2024
Viewed by 563
Abstract
Background/Objectives: Porcine Circovirus 2 (PCV2) infection poses significant health and economic challenges to the global swine industry. The disease in pigs leads to lymphoid depletion, resulting in immunosuppression and increased susceptibility to co-infections with other bacterial and viral pathogens. This study evaluated [...] Read more.
Background/Objectives: Porcine Circovirus 2 (PCV2) infection poses significant health and economic challenges to the global swine industry. The disease in pigs leads to lymphoid depletion, resulting in immunosuppression and increased susceptibility to co-infections with other bacterial and viral pathogens. This study evaluated the efficacy of two novel recombinant Newcastle disease virus (NDV) strain R2B vectored vaccines that express the cap gene of PCV2 alone and along with the transmembrane and cytoplasmic tail (TMCT) domains of the NDV F gene. The efficacy of the vaccine candidates was studied in mouse and pig models. Methods: Six-week-old BALB/c mice were divided into five groups and immunized intramuscularly three times at 14-day intervals with various vaccine candidates, namely rNDV-R2B-PCVcap-TMCT, rNDV-R2B-PCVcap, and CircoFLEX commercial vaccine, along with controls. Following immunization and PCV2d virus challenge, multiple assays assessed the immune responses in animal trials. In the pig animal trial, pigs were divided into four groups: a control group (PBS), NDV-vectored PCVcap-TMCT group, NDV-vectored-PCVcap group, and CircoFLEX vaccine group. Pigs were immunized intramuscularly twice at 28-day intervals. Blood samples were collected at regular intervals over 70 days to evaluate the humoral and cell-mediated immune responses. Results: Both mice and pigs’ trials indicated that the NDV-vectored PCV2 cap-TMCT vaccine candidate elicited superior immune responses. In mice, the rNDV-R2B-PCVcap-TMCT group showed enhanced humoral and cellular immunity, increased PCV2-specific antibody levels, higher CD4+/CD8+ ratio, elevated IFN-γ and TNF-α levels, decreased IL-10 levels, reduced viral loads, and minimal histopathological changes. In pigs, the NDV-vectored PCVcap-TMCT group demonstrated better antibody responses, cytokine profiles (IFN-γ and IL-10), and higher levels of PCV2-specific neutralizing antibodies against the PCV2a, PCV2b and PCV2d genotypes when compared to other groups. Conclusions: These findings suggest NDV-vectored PCVcap-TMCT vaccine candidate, expressing the cap gene of PCV2 along with the TMCT domain, offers a promising alternative for protecting against PCV2 infection, potentially addressing the challenges posed by emerging PCV2 strains in the swine industry. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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22 pages, 1010 KiB  
Review
Factors Predicting COVID-19 Vaccine Effectiveness and Longevity of Humoral Immune Responses
by Engin Berber and Ted M. Ross
Vaccines 2024, 12(11), 1284; https://doi.org/10.3390/vaccines12111284 - 15 Nov 2024
Viewed by 622
Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, prompted global efforts to develop vaccines to control the disease. Various vaccines, including mRNA (BNT162b2, mRNA-1273), adenoviral vector (ChAdOx1, Ad26.COV2.S), and inactivated virus platforms (BBIBP-CorV, CoronaVac), elicit high-titer, protective antibodies against the virus, but long-term antibody durability [...] Read more.
The COVID-19 pandemic, caused by SARS-CoV-2, prompted global efforts to develop vaccines to control the disease. Various vaccines, including mRNA (BNT162b2, mRNA-1273), adenoviral vector (ChAdOx1, Ad26.COV2.S), and inactivated virus platforms (BBIBP-CorV, CoronaVac), elicit high-titer, protective antibodies against the virus, but long-term antibody durability and effectiveness vary. The objective of this study is to elucidate the factors that influence vaccine effectiveness (VE) and the longevity of humoral immune responses to COVID-19 vaccines through a review of the relevant literature, including clinical and real-world studies. Here, we discuss the humoral immune response to different COVID-19 vaccines and identify factors influencing VE and antibody longevity. Despite initial robust immune responses, vaccine-induced immunity wanes over time, particularly with the emergence of variants, such as Delta and Omicron, that exhibit immune escape mechanisms. Additionally, the durability of the humoral immune responses elicited by different vaccine platforms, along with the identification of essential determinants of long-term protection—like pre-existing immunity, booster doses, hybrid immunity, and demographic factors—are critical for protecting against severe COVID-19. Booster vaccinations substantially restore neutralizing antibody levels, especially against immune-evasive variants, while individuals with hybrid immunity have a more durable and potent immune response. Importantly, comorbidities such as diabetes, cardiovascular disease, chronic kidney disease, and cancer significantly reduce the magnitude and longevity of vaccine-induced protection. Immunocompromised individuals, particularly those undergoing chemotherapy and those with hematologic malignancies, have diminished humoral responses and benefit disproportionately from booster vaccinations. Age and sex also influence immune responses, with older adults experiencing accelerated antibody decline and females generally exhibiting stronger humoral responses compared to males. Understanding the variables affecting immune protection is crucial to improving vaccine strategies and predicting VE and protection against COVID-19. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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3 pages, 1622 KiB  
Correction
Correction: Huang et al. Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection. Vaccines 2021, 9, 793
by Ying Huang, Monique S. França, James D. Allen, Hua Shi and Ted M. Ross
Vaccines 2024, 12(11), 1283; https://doi.org/10.3390/vaccines12111283 - 15 Nov 2024
Viewed by 247
Abstract
The authors would like to make the following corrections to this published paper [...] Full article
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24 pages, 2358 KiB  
Review
Milk-Derived Extracellular Vesicles: A Novel Perspective on Comparative Therapeutics and Targeted Nanocarrier Application
by Muttiah Barathan, Sook Luan Ng, Yogeswaran Lokanathan, Min Hwei Ng and Jia Xian Law
Vaccines 2024, 12(11), 1282; https://doi.org/10.3390/vaccines12111282 - 15 Nov 2024
Viewed by 624
Abstract
Milk-derived extracellular vesicles (mEVs) are emerging as promising therapeutic candidates due to their unique properties and versatile functions. These vesicles play a crucial role in immunomodulation by influencing macrophage differentiation and cytokine production, potentially aiding in the treatment of conditions such as bone [...] Read more.
Milk-derived extracellular vesicles (mEVs) are emerging as promising therapeutic candidates due to their unique properties and versatile functions. These vesicles play a crucial role in immunomodulation by influencing macrophage differentiation and cytokine production, potentially aiding in the treatment of conditions such as bone loss, fibrosis, and cancer. mEVs also have the capacity to modulate gut microbiota composition, which may alleviate the symptoms of inflammatory bowel diseases and promote intestinal barrier integrity. Their potential as drug delivery vehicles is significant, enhancing the stability, solubility, and bioavailability of anticancer agents while supporting wound healing and reducing inflammation. Additionally, bovine mEVs exhibit anti-aging properties and protect skin cells from UV damage. As vaccine platforms, mEVs offer advantages including biocompatibility, antigen protection, and the ability to elicit robust immune responses through targeted delivery to specific immune cells. Despite these promising applications, challenges persist, including their complex roles in cancer, effective antigen loading, regulatory hurdles, and the need for standardized production methods. Achieving high targeting specificity and understanding the long-term effects of mEV-based therapies are essential for clinical translation. Ongoing research aims to optimize mEV production methods, enhance targeting capabilities, and conduct rigorous preclinical and clinical studies. By addressing these challenges, mEVs hold the potential to revolutionize vaccine development and targeted drug delivery, ultimately improving therapeutic outcomes across various medical fields. Full article
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9 pages, 1116 KiB  
Perspective
The Immunologic Downsides Associated with the Powerful Translation of Current COVID-19 Vaccine mRNA Can Be Overcome by Mucosal Vaccines
by Maurizio Federico
Vaccines 2024, 12(11), 1281; https://doi.org/10.3390/vaccines12111281 - 14 Nov 2024
Viewed by 8693
Abstract
The action of mRNA-based vaccines requires the expression of the antigen in cells targeted by lipid nanoparticle–mRNA complexes. When the vaccine antigen is not fully retained by the producer cells, its local and systemic diffusion can have consequences depending on both the levels [...] Read more.
The action of mRNA-based vaccines requires the expression of the antigen in cells targeted by lipid nanoparticle–mRNA complexes. When the vaccine antigen is not fully retained by the producer cells, its local and systemic diffusion can have consequences depending on both the levels of antigen expression and its biological activity. A peculiarity of mRNA-based COVID-19 vaccines is the extraordinarily high amounts of the Spike antigen expressed by the target cells. In addition, vaccine Spike can be shed and bind to ACE-2 cell receptors, thereby inducing responses of pathogenetic significance including the release of soluble factors which, in turn, can dysregulate key immunologic processes. Moreover, the circulatory immune responses triggered by the vaccine Spike is quite powerful, and can lead to effective anti-Spike antibody cross-binding, as well as to the emergence of both auto- and anti-idiotype antibodies. In this paper, the immunologic downsides of the strong efficiency of the translation of the mRNA associated with COVID-19 vaccines are discussed together with the arguments supporting the idea that most of them can be avoided with the advent of next-generation, mucosal COVID-19 vaccines. Full article
(This article belongs to the Special Issue Efficacy, Immunogenicity and Safety of COVID-19 Vaccines and COVID-19 Vaccination Strategies)
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16 pages, 1091 KiB  
Review
Beyond Suppression: Peripheral T Cell Responses to Vaccination in Inflammatory Bowel Disease Patients Undergoing Anti-Tumor-Necrosis-Factor Therapy
by Martin Qui and Ennaliza Salazar
Vaccines 2024, 12(11), 1280; https://doi.org/10.3390/vaccines12111280 - 14 Nov 2024
Viewed by 616
Abstract
Alimentary tract inflammation in inflammatory bowel disease (IBD) is treated by systemically administered drugs that alter fundamental host immune responses. Biologics that target tumor necrosis factor (TNF) are first-line biologics in IBD, used widely for their effectiveness, steroid-sparing quality, and lower cost. While [...] Read more.
Alimentary tract inflammation in inflammatory bowel disease (IBD) is treated by systemically administered drugs that alter fundamental host immune responses. Biologics that target tumor necrosis factor (TNF) are first-line biologics in IBD, used widely for their effectiveness, steroid-sparing quality, and lower cost. While they enable a significant proportion of patients to achieve clinical remission, they carry an increased risk of infection and poor serological responses to vaccination. Conversely, our understanding of adaptive T cell responses in anti-TNF-treated IBD patients remains limited. The introduction of COVID-19 vaccines has prompted research that both challenges and refines our view on immunomodulatory therapy and its potential implications for immunity and protection. Here, we review these emergent findings, evaluate how they shape our understanding of vaccine-induced T cell responses in the context of anti-TNF therapy in IBD, and provide a perspective highlighting the need for a holistic evaluation of both cellular and humoral immunity in this population. Full article
(This article belongs to the Special Issue Immune Responses in Patients with Inflammatory Bowel Disease after Vaccination)
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11 pages, 991 KiB  
Article
The Health and Economic Effects of PCV15 and PCV20 During the First Year of Life in the US
by Aleksandar Ilic, Maria J. Tort, Alejandro Cane, Raymond A. Farkouh and Mark H. Rozenbaum
Vaccines 2024, 12(11), 1279; https://doi.org/10.3390/vaccines12111279 - 14 Nov 2024
Viewed by 442
Abstract
(1) Background/Objectives: Two pneumococcal conjugate vaccines, 15-(PCV15) and 20-(PCV20) valent formulations, are routinely recommended for US children in a 3+1 schedule. The first three doses are administered during the first year of life at 2, 4, and 6 months, while a booster dose [...] Read more.
(1) Background/Objectives: Two pneumococcal conjugate vaccines, 15-(PCV15) and 20-(PCV20) valent formulations, are routinely recommended for US children in a 3+1 schedule. The first three doses are administered during the first year of life at 2, 4, and 6 months, while a booster dose is given at 12 to 15 months. This study evaluated the health and economic effects of the PCV20 infant series within the first year of life compared to PCV15. (2) Methods: Using a decision-analytic model, we calculated the health and economic effects of introducing PCV15 or PCV20 for five subsequent birth cohorts. Epidemiological data were drawn from peer-reviewed studies and estimates for vaccine effectiveness were extrapolated from established PCV13 effectiveness and PCV7 efficacy studies. Direct medical costs related to the disease treatment were extracted from the literature and inflated to 2024 dollars. (3) Results: Over the course of five years, the implementation of PCV20 vaccination for newborns in the United States, compared to PCV15, is projected to prevent an additional 220 cases of invasive pneumococcal disease, 6542 cases of community-acquired pneumonia, and 112,095 cases of otitis media within the first year of life across five subsequent birth cohorts. This strategy could prevent 66 infant deaths linked to these illnesses and confer extra health gains, amounting to 5058 years of life and 5037 quality-adjusted life years. These prevented cases are estimated to save approximately USD 147 million over 5 years. (4) Conclusions: This study demonstrated that vaccinating with PCV20 during the first 12 months of life compared to PCV15 in the US would yield a substantially greater health and economic return due to the five additional serotypes covered by PCV20. Full article
(This article belongs to the Special Issue The Effectiveness of Pneumococcal Conjugate Vaccines)
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16 pages, 1281 KiB  
Review
Host Innate and Adaptive Immunity Against African Swine Fever Virus Infection
by Tianqi Zhang, Zixun Lu, Jia Liu, Yang Tao, Youhui Si, Jing Ye, Shengbo Cao and Bibo Zhu
Vaccines 2024, 12(11), 1278; https://doi.org/10.3390/vaccines12111278 - 13 Nov 2024
Viewed by 544
Abstract
Africa swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious hemorrhagic disease that can result in up to 100% lethality in both wild and domestic swine, regardless of breed or age. The ongoing ASF pandemic poses [...] Read more.
Africa swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious hemorrhagic disease that can result in up to 100% lethality in both wild and domestic swine, regardless of breed or age. The ongoing ASF pandemic poses significant threats to the pork industry and food security, with serious implications for the sanitary and socioeconomic system. Due to the limited understanding of ASFV pathogenesis and immune protection mechanisms, there are currently no safe and effective vaccines or specific treatments available, complicating efforts for prevention and control. This review summarizes the current understanding of the intricate interplay between ASFV and the host immune system, encompassing both innate and adaptive immune responses to ASFV infection, as well as insights into ASFV pathogenesis and immunosuppression. We aim to provide comprehensive information to support fundamental research on ASFV, highlighting existing gaps and suggesting future research directions. This work may serve as a theoretical foundation for the rational design of protective vaccines against this devastating viral disease. Full article
(This article belongs to the Special Issue Adaptive and Innate Response to Viral Disease)
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15 pages, 951 KiB  
Article
Heterogeneous Associations Between Pandemic-Induced Socioeconomic Hardships and COVID-19 Vaccine Uptake by Sexual Orientation and Gender Identity: A Nationally Representative Analysis in the United States
by JungHo Park and Byoungjun Kim
Vaccines 2024, 12(11), 1277; https://doi.org/10.3390/vaccines12111277 - 13 Nov 2024
Viewed by 473
Abstract
Background/Objectives: Socioeconomic hardship during the COVID-19 pandemic was associated with lower vaccine uptake. Since the pandemic has exacerbated socioeconomic challenges faced by sexual and gender minority populations, including employment income loss, housing instability, food insufficiency, and household expense difficulty, this study investigated the [...] Read more.
Background/Objectives: Socioeconomic hardship during the COVID-19 pandemic was associated with lower vaccine uptake. Since the pandemic has exacerbated socioeconomic challenges faced by sexual and gender minority populations, including employment income loss, housing instability, food insufficiency, and household expense difficulty, this study investigated the disparities in COVID-19 vaccine uptake among these populations. Methods: Using the U.S. Census Bureau Household Pulse Survey, a nationally representative sample of 1,767,966 individuals (6% gay or lesbian, 4.2% bisexual, 1.6% something else, and 90.6% heterosexual respondents), we quantified the COVID-19 vaccine uptakes among sexual and gender minorities, as well as the effect measure modifications by socioeconomic hardships. Results: Despite higher vaccine uptake rates among sexual and gender minorities compared to their heterosexual counterparts, socioeconomic hardships triggered by the pandemic among these populations were associated with decreased vaccine uptake. Importantly, the effect measure modifications by socioeconomic hardships were more pronounced among sexual and gender minority status compared to heterosexual individuals. Conclusions: These results highlight the critical need to address socioeconomic hardships among sexual and gender minorities to enhance vaccine uptake, along with the pre-existing and exacerbated social and economic disadvantages during the COVID-19 pandemic. Full article
(This article belongs to the Special Issue Factors That Contribute to Vaccine Hesitancy towards COVID-19 Vaccination)
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13 pages, 1563 KiB  
Article
Hepatitis A Seroprevalence Among HIV-Exposed and Unexposed Pediatric Populations in South Africa
by Edina Amponsah-Dacosta, Lufuno Ratshisusu, Lorato M. Modise, Ntombifuthi Blose, Omphile E. Simani, Selokela G. Selabe, Benjamin M. Kagina and Rudzani Muloiwa
Vaccines 2024, 12(11), 1276; https://doi.org/10.3390/vaccines12111276 - 13 Nov 2024
Viewed by 647
Abstract
Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were [...] Read more.
Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4–25) months. The median maternal age was 29 (IQR: 25–34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2–98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1–25.7]), while 1.1% (2/188 [95% CI 0.12–2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4–86.3] and HEU = 45%, 9/20 [95% CI 23.8–68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4–37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood. Full article
(This article belongs to the Special Issue Vaccines and Vaccination: HIV, Hepatitis Viruses, and HPV)
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19 pages, 3136 KiB  
Article
An Optimised Live Attenuated Influenza Vaccine Ferret Efficacy Model Successfully Translates H1N1 Clinical Data
by Katarzyna E. Schewe, Shaun Cooper, Jonathan Crowe, Steffan Llewellyn, Lydia Ritter, Kathryn A. Ryan and Oliver Dibben
Vaccines 2024, 12(11), 1275; https://doi.org/10.3390/vaccines12111275 - 13 Nov 2024
Viewed by 627
Abstract
Between 2013 and 2016, the A/H1N1pdm09 component of the live attenuated influenza vaccine (LAIV) produced instances of lower-than-expected vaccine effectiveness. Standard pre-clinical ferret models, using a human-like vaccine dose and focusing on antigenic match to circulating wildtype (wt) strains, were unable [...] Read more.
Between 2013 and 2016, the A/H1N1pdm09 component of the live attenuated influenza vaccine (LAIV) produced instances of lower-than-expected vaccine effectiveness. Standard pre-clinical ferret models, using a human-like vaccine dose and focusing on antigenic match to circulating wildtype (wt) strains, were unable to predict these fluctuations. By optimising the vaccine dose and utilising clinically relevant endpoints, we aimed to develop a ferret efficacy model able to reproduce clinical observations. Ferrets were intranasally vaccinated with 4 Log10 FFU/animal (1000-fold reduction compared to clinical dose) of seven historical LAIV formulations with known (19–90%) H1N1 vaccine efficacy or effectiveness (VE). Following homologous H1N1 wt virus challenge, protection was assessed based on primary endpoints of wt virus shedding in the upper respiratory tract and the development of fever. LAIV formulations with high (82–90%) H1N1 VE provided significant protection from wt challenge, while formulations with reduced (19–32%) VE tended not to provide significant protection. The strongest correlation observed was between reduction in wt shedding and VE (R2 = 0.75). Conversely, serum immunogenicity following vaccination was not a reliable indicator of protection (R2 = 0.37). This demonstrated that, by optimisation of the vaccine dose and the use of non-serological, clinically relevant protection endpoints, the ferret model could successfully translate clinical H1N1 LAIV VE data. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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13 pages, 2670 KiB  
Article
Immunity Dynamics of Neisseria meningitidis Serogroups ACYW from Birth and Following Vaccination
by Lilian Zeng, Yingyin Deng, Chumin Liang, Zixia Qian, Yueling Chen, Huifang Lin, Runyu Yuan, Pingping Zhou, Xue Zhuang, Ying Yang, Qi Zhu, Limei Sun, Jianfeng He and Jiufeng Sun
Vaccines 2024, 12(11), 1274; https://doi.org/10.3390/vaccines12111274 - 13 Nov 2024
Viewed by 530
Abstract
Background: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. Methods: We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in [...] Read more.
Background: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. Methods: We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in Guangdong Province, measuring Anti-Nm IgG with serogroups A, C, Y, and W, and analyzed the trends using a generalized additive model (GAM). Results: During 2019–2022, 7752 participants were included. The overall antibody positivity rate for serogroups A, C, Y, and W were 60.75%, 15.51%, 32.83%, and 14.56%, respectively. High Anti-Nm IgG was in children aged 0–5 and 5–10 years old. Geometric mean concentrations (GMCs) of Anti-Nm IgG were higher and correlated positively with vaccine doses compared with unvaccinated individuals. The GMC showed a consistent decrease trend in the vaccinated and a U-shaped curve in populations. The declined rates of GMC were 1.59 (95% CI: 1.03, 2.14) µg/mL, 1.65 (95% CI: 1.28, 2.03), 0.62 (95% CI: 0.22, 1.03), and 0.31 (95% CI: 0.08, 0.53) µg/mL per year for serogroups A, C, Y, and W, respectively. Conclusions: There were differences in antibody positivity rate and GMC for the four serogroups of ECM in the healthy individuals of Guangdong Province, with serogroup A showing the highest, and the demographic differences highlighted the high seroprevalence of Neisseria meningitidis in younger people. The variable prevalence rates among serogroups A, C, Y, and W and the observed decline in antibody titers underscore the need for adjustments in the immunization program targeting the meningococcal vaccine. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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19 pages, 1436 KiB  
Article
Vaccination Against Androgen Receptor Splice Variants to Immunologically Target Prostate Cancer
by Robert D. Marek, Selena Halabi, Mu-En Wang, Jason McBane, Junping Wei, Tao Wang, Xiao Yang, Congxiao Liu, Gangjun Lei, Herbert Kim Lyerly, Ming Chen, Timothy N. Trotter and Zachary C. Hartman
Vaccines 2024, 12(11), 1273; https://doi.org/10.3390/vaccines12111273 - 13 Nov 2024
Viewed by 503
Abstract
Background/Objectives: Androgen receptor (AR) expression and signaling are critical for the progression of prostate cancer and have been the therapeutic focus of prostate cancer for over 50 years. While a variety of agents have been developed to target this axis, many of [...] Read more.
Background/Objectives: Androgen receptor (AR) expression and signaling are critical for the progression of prostate cancer and have been the therapeutic focus of prostate cancer for over 50 years. While a variety of agents have been developed to target this axis, many of these fail due to the emergent expression of AR RNA splice variants, such as AR-V7, that can signal independently of ligand binding. Other therapies, such as vaccination against prostate-specific antigens, have achieved FDA approvals but have fallen short of being incorporated as standard-of-care therapies for advanced prostate cancer. This may be due to the elevated level of immunosuppression observed in prostate cancer, which remains largely refractory to immune checkpoint blockade. Methods: We developed a vaccine targeting AR-V7, a common isoform associated with treatment resistance, and demonstrated its ability to elicit AR-V7-specific immunity and enable anti-tumor responses against AR-V7+ cancers in subcutaneous tumor models. Results: Our studies also revealed that AR-V7 expression conferred an immune suppressive phenotype that was significant in a non-AR-dependent prostate cancer model. Notably, in this model, we found that vaccination in combination with enzalutamide, an AR antagonist, suppressed these aggressive immune suppressive cancers and resulted in enhanced survival in comparison to control vaccinated and enzalutamide-treated mice. While anti-PD-1 immune checkpoint inhibition (ICI) alone slowed tumor growth, the majority of vaccinated mice that received anti-PD-1 therapy showed complete tumor elimination. Conclusions: Collectively, these results validate the importance of AR signaling in prostate cancer immune suppression and suggest the potential of AR-V7-specific vaccines as therapeutic strategies against prostate cancer, offering significant protective and therapeutic anti-tumor responses, even in the presence of androgen signaling inhibitors. Full article
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15 pages, 2009 KiB  
Article
Design of a Glycoconjugate Vaccine Against Salmonella Paratyphi A
by Renzo Alfini, Martina Carducci, Luisa Massai, Daniele De Simone, Marco Mariti, Omar Rossi, Simona Rondini, Francesca Micoli and Carlo Giannelli
Vaccines 2024, 12(11), 1272; https://doi.org/10.3390/vaccines12111272 - 12 Nov 2024
Viewed by 517
Abstract
Background/Objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against S. [...] Read more.
Background/Objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against S. Paratyphi A. Here we describe the design of a S. Paratyphi A conjugate. Methods: The serovar-specific O-antigen (O:2) was linked to the CRM197 carrier protein (O:2–CRM197) and a panel of conjugates differing for structural characteristics were compared in mice and rabbits. Results: We identified the O-antigen molecular size, polysaccharide to protein ratio, conjugate cross-linking, and O:2 O-acetylation level as critical quality attributes and identified optimal design for a more immunogenic vaccine. Conclusions: This work guides the development of the O:2–CRM197 conjugate to be combined with TCV in a bivalent formulation against enteric fever. Full article
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14 pages, 4020 KiB  
Article
Efficacy of Feed-Based Genome-Free Bacterial Vaccine Against Aeromonas hydrophila Infection in Red Tilapia (Oreochromis sp.)
by Nur Shidaa Mohd Ali, Mohamad Syazwan Ngalimat, Boon Chuan Lim, Chia-Chen Hsu, Annas Salleh, Muhammad Farhan Nazarudin, Ina Salwany Md Yasin and Mohammad Noor Amal Azmai
Vaccines 2024, 12(11), 1271; https://doi.org/10.3390/vaccines12111271 - 11 Nov 2024
Viewed by 530
Abstract
Aeromonas hydrophila causes motile Aeromonas septicemia (MAS), a disease with a high mortality rate in tilapia culture. Feed-based vaccines with the incorporation of inactivated whole-cell bacteria into the feed offer promising tools to control MAS. Currently, the incorporation of genome-free bacteria as bacterial [...] Read more.
Aeromonas hydrophila causes motile Aeromonas septicemia (MAS), a disease with a high mortality rate in tilapia culture. Feed-based vaccines with the incorporation of inactivated whole-cell bacteria into the feed offer promising tools to control MAS. Currently, the incorporation of genome-free bacteria as bacterial vaccine through the implementation of SimCells® technology into the feed has become a particular interest. Background/Objectives: This study investigates the efficacy of a feed-based vaccine incorporating genome-free A. hydrophila (FBV-GFAH) against MAS infection in red tilapia. Methods: The vaccine was prepared and delivered at 5% fish body weight for three consecutive days in weeks 0 (prime vaccination) and 2 (first booster vaccination), orally. Throughout a five-week experimental period, the immune-related genes (IL-1β, MHC-II, CD4, IgT, and IgM) expression in the hindgut and head kidney of the fish was determined using RT-qPCR assay. Lysozyme (serum) and overall IgM (serum, gut lavage, and skin mucus) productions were also detected. Results: Fish vaccinated with FBV-GFAH showed a significant (p ≤ 0.05) improvement in relative percent survival compared with unvaccinated fish following bacterial challenge. FBV-GFAH induced the expression of immune-related genes in the hindgut and head kidney, especially after booster vaccination. Furthermore, serum lysozyme activity and overall IgM production in serum, skin mucus, and gut lavage were also significantly (p ≤ 0.05) improved in the FBV-GFAH vaccinated fish than the unvaccinated fish. Conclusions: This study showed that FBV-GFAH is a promising feed-based vaccine technology to control MAS in cultured tilapia. Full article
(This article belongs to the Special Issue Fish Disease Occurrence and Immune Prevention and Control)
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12 pages, 2248 KiB  
Review
Immune Checkpoint Inhibitors and Vaccination: Assessing Safety, Efficacy, and Synergistic Potential
by Jacob New, Luke Shenton, Radia Ksayer, Justin Wang, Karam Zakharia, Laura J. Nicholson and Amitabh C. Pandey
Vaccines 2024, 12(11), 1270; https://doi.org/10.3390/vaccines12111270 - 11 Nov 2024
Viewed by 715
Abstract
Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients—largely developed in the [...] Read more.
Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients—largely developed in the context of cytotoxic therapies—becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce. Notably, the combination of ICIs with infectious disease vaccines does not appear to exacerbate immune-related adverse events, despite the heightened cytokine activity observed. However, the efficacy of vaccines administered alongside ICIs in preventing infectious diseases remains poorly supported by robust evidence. Preliminary findings suggest a potential survival benefit in cancer patients receiving ICI therapy alongside influenza or SARS-CoV-2 vaccination, though the quality of evidence is currently low. Moreover, the synergistic potential of combining therapeutic cancer vaccines, particularly mRNA-based vaccines, with ICIs indicates promise but with a paucity of phase III data to confirm efficacy. This review critically examines the safety and efficacy of combining ICIs with both infectious disease vaccines and therapeutic cancer vaccines. While vaccination appears safe in patients undergoing ICI therapy, the impact on infectious disease prevention and cancer treatment outcomes warrants further rigorous investigation. Full article
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Article
The Impact of Palivizumab for Respiratory Syncytial Virus Prophylaxis on Preschool Childhood Asthma
by Hannah Ora Hasson, Yoav Bachar, Itai Hazan, Inbal Golan-Tripto, Aviv Goldbart, David Greenberg and Guy Hazan
Vaccines 2024, 12(11), 1269; https://doi.org/10.3390/vaccines12111269 - 10 Nov 2024
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Abstract
Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma [...] Read more.
Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization. Full article
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