Challenges to Developing New Vaccines and Improving Existing Platforms

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: 31 January 2027 | Viewed by 10930

Special Issue Editor


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Guest Editor
1. School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, UK
2. Virology, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, UK
Interests: pathogenic mechanisms of RNA viruses (morbilliviruses, respiratory syncytial virus, coronavirus); recombinant vaccine design; genetic markers of virus susceptibility and assessment in small/large animal models; paramyxoviruses; pathogenic mechanisms of measles virus; morbilliviruses; respiratory syncytial virus; coronavirus; vaccine design; vaccination
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Special Issue Information

Dear Colleagues,

The science community faces significant challenges in developing new vaccines and enhancing existing vaccine platforms for infectious diseases and cancer. This Special Issue will address the following aspects of vaccines and their development:

  • Vaccine delivery for human and animal species for infectious diseases and cancer.
  • Advances in vaccine design that provide broad protection and stimulate humoral and cellular immunity.
  • Combining inactivated and subunit vaccines with long-acting adjuvants to maximize their effectiveness.
  • Development of novel assays, e.g., omics-based approaches, to evaluate comprehensive and early responses to vaccination.
  • Overcoming obstacles in developing flavivirus vaccines, e.g., dengue viruses, addressing virus serotypes, and preventing antibody-dependent enhancement.

We eagerly anticipate your contributions.

Prof. Dr. S. Louise Cosby
Guest Editor

Manuscript Submission Information

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Keywords

  • infectious disease
  • cancer vaccines
  • humoral and cellular immunity
  • flaviviruses vaccines
  • inactivated and subunit vaccines
  • novel assays

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Published Papers (6 papers)

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Research

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24 pages, 51034 KB  
Article
Exploring the Vaccine Adjuvant Effect and Mechanism of Epimedium Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations
by Meng Tang, Anni Zhao, Yun Yang, Zhen Song, Sheng Wang, Xianghao Ye, Haozheng Luo, Liqun Zhao, Jiale Pan, Quanming Zou, Hongwu Sun and Hao Zeng
Vaccines 2026, 14(5), 385; https://doi.org/10.3390/vaccines14050385 - 26 Apr 2026
Viewed by 340
Abstract
Background: Epimedium is a natural herb with immunomodulatory potential, but its vaccine adjuvant properties remain poorly understood. Objective: The aim of this study was to elucidate the adjuvant effects of Epimedium and the underlying molecular mechanisms. Methods: Network pharmacology was used to [...] Read more.
Background: Epimedium is a natural herb with immunomodulatory potential, but its vaccine adjuvant properties remain poorly understood. Objective: The aim of this study was to elucidate the adjuvant effects of Epimedium and the underlying molecular mechanisms. Methods: Network pharmacology was used to identify bioactive compounds and targets of Epimedium from the TCMSP database, and immunomodulation-related targets from GeneCards and OMIM. PPI networks, KEGG/GO enrichment, molecular docking, and molecular dynamics (MD) simulations were performed. In vivo, female BALB/c mice were immunized with the Staphylococcus aureus (S. aureus) vaccine subunit HI antigen, either alone or with low- or high-dose icariin (ICA). Serum antibody responses (IgG, IgG1, IgG2a, IgG2b) were measured by ELISA. Survival against lethal S. aureus USA300 challenge was monitored. Results: Network pharmacology predicted 488 targets and 13 pathways. Core targets included IL6, TP53, EGFR, CTNNB1, HIF1A, HSP90AA1, JUN, MTOR, SRC, and AKT1. KEGG/GO analysis indicated involvement of T cell receptor and NOD-like receptor signaling pathways in inflammatory responses. Molecular docking and MD simulations confirmed stable ligand-target binding. Experimental validation showed that ICA significantly enhanced HI-specific antibody responses and induced a Th2-biased humoral immune response (IgG1/IgG2a ratio > 1), which is particularly relevant for vaccines targeting extracellular pathogens such as S. aureus. ICA also improved survival after lethal bacterial challenge. Conclusions: This study identifies potential bioactive compounds, core targets, and key pathways of Epimedium as a vaccine adjuvant. Experimentally, ICA, as a representative component, enhanced HI-specific antibody responses and conferred protection against lethal S. aureus challenge. Together, these findings offer a computational–experimental basis that may guide further mechanistic investigation. Full article
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17 pages, 1961 KB  
Article
Nanoparticle Vaccines Based on the Truncated VZV gE Elicit a Robust Immune Response in Mice
by Tianxin Shi, Hai Li, Jiehui Wu, Hongqiao Hu, Jie Jiang, Ruichen Wang, Ziyi Li, Qianqian Cui, Shihong Fu, Kai Nie, Fan Li, Qikai Yin, Huanyu Wang and Songtao Xu
Vaccines 2026, 14(1), 69; https://doi.org/10.3390/vaccines14010069 - 7 Jan 2026
Cited by 1 | Viewed by 1056
Abstract
Background: Herpes zoster (HZ), caused by the reactivation of varicella-zoster virus (VZV), primarily affects elderly populations worldwide. Although current recombinant HZ vaccines show strong immunogenicity, their high cost and potential side effects may limit their widespread use. Therefore, developing a cost-effective HZ vaccine [...] Read more.
Background: Herpes zoster (HZ), caused by the reactivation of varicella-zoster virus (VZV), primarily affects elderly populations worldwide. Although current recombinant HZ vaccines show strong immunogenicity, their high cost and potential side effects may limit their widespread use. Therefore, developing a cost-effective HZ vaccine with improved safety profiles would have significant clinical and public health implications. Methods: Building upon our previously optimized truncated gE (tgE350) from VZV, we developed the tgE350 + Fe nanoparticle vaccine using SpyTag/SpyCatcher covalent conjugation. The tgE350 protein (with a SpyTag tag) and the Fe protein (with a SpyCatcher tag) were expressed in HEK293F and E. coli BL21, respectively, enabling spontaneous nanoparticle assembly. Protein expression and nanoparticle formation were confirmed through SDS-PAGE and negative-stain electron microscopy. BALB/c mice were inoculated with either tgE350 + Fe or tgE350 combined with Al and CpG adjuvants. Immune responses were evaluated using ELISpot and flow cytometry for cellular immunity, along with ELISA, VZV microneutralization, and fluorescent antibody membrane antigen (FAMA) assays for antibody titers. Histopathological examination of major organs ensured vaccine safety. Results: Compared with the truncated vaccine tgE350, the nanoparticle vaccine tgE350 + Fe significantly enhanced VZV neutralizing antibodies and specific antibody responses in mice without causing significant changes in lymphocyte populations (no difference from the control group). Moreover, the tgE350 + Fe group had significantly more lymphocytes secreting IFN-γ, IL-2, and IL-4 than the tgE350 group. No apparent pathological damage was observed in the heart, liver, spleen, or lungs of mice in any experimental group. Conclusions: This experiment successfully developed the HZ nanoparticle vaccine tgE350 + Fe. It enhanced VZV-specific neutralizing antibodies, generated better cellular and humoral immune responses, and demonstrated good safety. Full article
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22 pages, 2697 KB  
Article
A Cyclic-di-AMP Adjuvanted CPAF Protein Vaccine Is Immunogenic in Swine, but It Fails to Reduce Genital Chlamydia trachomatis Burden
by Leonie Bettin, Maria Stadler, Christine Unterweger, Maximiliane Dippel, Jonathan M. Harris, Andrea Buzanich-Ladinig, Taylor B. Poston, Toni Darville and Tobias Käser
Vaccines 2025, 13(5), 468; https://doi.org/10.3390/vaccines13050468 - 27 Apr 2025
Cited by 2 | Viewed by 2346
Abstract
Background/ObjectivesChlamydia trachomatis (Ct) is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite the high prevalence and [...] Read more.
Background/ObjectivesChlamydia trachomatis (Ct) is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite the high prevalence and potential for serious health complications, no vaccine has been licensed. Pigs offer a valuable biomedical model for chlamydia research: they have an overall high degree of similarity to humans and serve as natural hosts for Chlamydia suis (Cs), a close relative of Ct. Thus, in this study, the pig model was used to evaluate a vaccine candidate against Ct. Methods: The vaccine candidate consists of chlamydial-protease-like activity factor (CPAF) protein adjuvanted with STING (Stimulator of Interferon Genes) pathway agonist cyclic-di-AMP (c-di-AMP). Pigs received two doses intramuscularly followed by two intranasal doses. Each week, the systemic T cell response was assessed via IFN-γ and IL-17 ELISpots, as well as multi-parameter flow cytometry on 0, 14, and 28 days post vaccination (dpv). The humoral immune response was analyzed by measuring CPAF-specific antibody levels and avidity via ELISAs. Results: Vaccination with c-di-AMP adjuvanted CPAF triggered low-level systemic IFN-γ and multifunctional IFN-γ+TNF-α+ CD4 T cell responses. Despite the rather low systemic effector cytokine production, robust anti-CPAF IgG responses were detected in serum, vaginal swab eluates, and oviduct flushes. Genital Ct challenge 42 dpv resulted in only transient infection, precluding a confident assessment of vaccine efficacy of the tested CPAF/c-di-AMP vaccine candidate. However, after challenge, vaccinated pigs exhibited boosted systemic anti-CPAF IFN-γ and mucosal IgG responses compared to unvaccinated pigs. Conclusions: Thus, while vaccine efficacy remains elusive, the CPAF/c-di-AMP vaccine candidate was immunogenic: it elicited a low-level systemic cell-mediated response and robust humoral immune responses. Future studies will incorporate a STING agonist directly conjugated to CPAF as well as addition of other Th1-inducing adjuvants to enhance cellular immunity. Full article
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Review

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18 pages, 686 KB  
Review
Clinical Evaluation of Allergen Immunotherapy for Allergic Rhinitis
by Francesco Catamerò, Maria Chiara Bragato, Montserrat Alvaro Lozano, Giorgio Walter Canonica, Domingo Barber Hernández, Maria M. Escribese, Enrico Heffler, Oliver Pfaar, Umit Sahiner, Giovanni Paoletti and Mattia Giovannini
Vaccines 2026, 14(4), 326; https://doi.org/10.3390/vaccines14040326 - 7 Apr 2026
Viewed by 2002
Abstract
Background/Objectives: Allergen immunotherapy (AIT), involving subcutaneous (SCIT) or sublingual (SLIT) administration of the culprit allergen, is the only treatment capable of modifying the natural course of allergic diseases, and provides lasting benefits in terms of symptom reduction and medication use. AIT for [...] Read more.
Background/Objectives: Allergen immunotherapy (AIT), involving subcutaneous (SCIT) or sublingual (SLIT) administration of the culprit allergen, is the only treatment capable of modifying the natural course of allergic diseases, and provides lasting benefits in terms of symptom reduction and medication use. AIT for allergic rhinitis is acknowledged as safe and effective in both adults and children; however, no studies have comprehensively evaluated the safety and efficacy of AIT in these populations, integrating results from randomized controlled trials (RCTs) and real-world evidence (RWE). Methods: We evaluated data in the literature including studies from RCTs and RWE in which the safety and efficacy of AIT in both children and adults have been analyzed. A narrative literature search was conducted in PubMed up to January 2026 using the following keywords for the search string: “allergen immunotherapy,” “AIT,” “safety,” “efficacy,” “clinical outcome,” and “clinical evaluation.” Results: RCTs and meta-analyses showed that both SCIT and SLIT significantly reduced allergic symptoms and medication use and improved quality of life (QoL). Large SLIT tablet trials have confirmed its efficacy in adults and children, whereas RWE supports its effectiveness in broader populations. Safety data indicated that SCIT carries a small but higher risk of systemic reactions than SLIT, which mainly causes mild local effects. Conclusions: AIT was effective and safe for treating allergic rhinitis across RCT and RWE studies. Integrating RWE with RCT findings is essential for guideline development, particularly for capturing long-term outcomes and real-world applications. Full article
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18 pages, 691 KB  
Review
Vaccination Against Respiratory Infections in Adults with Cancer: A Concise Guide for Clinicians
by Kay Choong See
Vaccines 2026, 14(1), 105; https://doi.org/10.3390/vaccines14010105 - 21 Jan 2026
Cited by 1 | Viewed by 1051
Abstract
Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly [...] Read more.
Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly significant role. These infections not only reduce life expectancy but can also delay cancer therapy, negatively affect treatment outcomes, and increase healthcare costs. In recent years, the burden of respiratory infections in this population has been driven by influenza virus, SARS-CoV-2, respiratory syncytial virus, Streptococcus pneumoniae, and Bordetella pertussis. Effective vaccines are available for all these pathogens and are recommended for adults with cancer, yet vaccination uptake remains suboptimal despite their heightened vulnerability. This review provides practical guidance for healthcare professionals on vaccinating adults with cancer against respiratory infections, summarizing key information to help clinicians address vaccination-related complacency, confidence, and convenience. Evidence from studies in both the general population and cancer patients consistently shows that vaccination benefits outweigh potential risks, with adverse event rates comparable to those seen in individuals without cancer. Early vaccination is encouraged, as there is limited justification for delaying immunization even when immune responses may be reduced. Vaccine dosing aligns with recommendations for the general population, with important exceptions. Live attenuated vaccines should be avoided because of the risk of replication and disease in immunocompromised patients, and selected groups may require booster doses to achieve adequate protection. Notably, cancer immunotherapy does not appear to impair vaccine-induced immune responses. Full article
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Other

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7 pages, 158 KB  
Commentary
Strengthening National Regulatory Authorities in Africa: A Critical Step Towards Enhancing Local Manufacturing of Vaccines and Health Products
by Alemayehu Duga, Nebiyu Dereje, Mosoka Papa Fallah, Tedi Angasa, Abebe Genetu Bayih, Edinam Agbenu, Ngashi Ngongo, Raji Tajudeen and Jean Kaseya
Vaccines 2025, 13(6), 646; https://doi.org/10.3390/vaccines13060646 - 16 Jun 2025
Cited by 7 | Viewed by 2662
Abstract
The World Health Organization (WHO) Global Benchmarking Tool (GBT) classifies regulatory systems into four maturity levels, with Maturity Level 3 (ML3) signifying a stable and effective regulatory environment. As of January 2025, eight African nations—Egypt, Ghana, Nigeria, Rwanda, Senegal, South Africa, Tanzania, and [...] Read more.
The World Health Organization (WHO) Global Benchmarking Tool (GBT) classifies regulatory systems into four maturity levels, with Maturity Level 3 (ML3) signifying a stable and effective regulatory environment. As of January 2025, eight African nations—Egypt, Ghana, Nigeria, Rwanda, Senegal, South Africa, Tanzania, and Zimbabwe—have attained ML3 status, marking a significant milestone in the continent’s regulatory landscape. Achieving ML3 confers critical benefits, including reducing substandard and falsified medicines, which enhances public health safety and fosters trust in healthcare systems. This progress encourages local manufacturing, diminishing reliance on imported medicines and promoting economic development. Furthermore, ML3 NRAs are better equipped to address public health emergencies, enabling swift approvals for vaccines and therapeutics while upholding safety standards. Nonetheless, challenges persist, including fragmented regulatory systems, the prevalence of counterfeit medicines, and limited resources. Overcoming these hurdles necessitates enhanced organizational capacity, investments in training, and the promotion of collaboration among NRAs. There is an urgent call for greater political commitment and resource allocation to strengthen regulatory systems across Africa. Achieving and maintaining ML3 status is essential for enhancing medicine regulation, supporting local manufacturing, and improving public health outcomes across the continent. While progress has been made, sustained efforts are crucial to tackling existing challenges and harnessing the full potential of advanced regulatory frameworks. Full article
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