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  • Open access
  • 8 Reads
Challenges and Prospects of Vectored Vaccine Platforms in the Nigerian Public Health System
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Published: 21 November 2025 by MDPI in The 3rd International Online Conference on Vaccines session Vectored Vaccines

Background:

Nigeria faces ongoing public health challenges from emerging and re-emerging viral infections, including Lassa fever, yellow fever, and COVID-19. In such settings, conventional vaccine strategies have often proven insufficient for timely outbreak response. Viral-vectored vaccines offer a promising alternative due to their strong immunogenicity, single-dose potential, and scalability.

Objective:

This review aims to assess the key challenges and future opportunities for integrating viral vectored vaccine platforms into Nigeria’s public health system.

Methods:

A secondary data review was conducted using peer-reviewed literature, national reports, and global health databases published between 2020 and 2024. Sources were selected based on relevance to vectored vaccines, public health infrastructure, and infectious disease response in Nigeria.

Results:

The review identified major obstacles to adoption, including limited local vaccine manufacturing capacity, cold-chain infrastructure gaps, and regulatory delays. Public trust and misinformation also remain significant barriers. However, recent successes with vectored vaccines for Ebola and COVID-19 in Africa suggest high potential for broader use. Nigeria’s growing biomedical research capacity, combined with strategic partnerships, could enhance deployment in future outbreaks.

Conclusion:

Despite infrastructural and regulatory challenges, vectored vaccine platforms have significant potential in Nigeria. Advancing their adoption will require investment in local production, community engagement, and streamlined approval processes. These efforts can improve epidemic preparedness and health system resilience.

  • Open access
  • 9 Reads
The Receptor binding domain 2 (RBD2) of binary toxin (CDT) as a promising vaccine candidate protects both mice and hamsters against CDT challenge
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Published: 21 November 2025 by MDPI in The 3rd International Online Conference on Vaccines session Vectored Vaccines

Clostridioides difficile infection (CDI) is primarily driven by two protein toxins, toxin A (TcdA) and toxin B (TcdB). Additionally, about 5–30% of C. difficile strains produce a third toxin, binary toxin (CDT), which is linked to higher morbidity and mortality rates in CDI. Vaccination is a cost effective approcah to prevent CDI. Current;y, no vaccine has been licenced against CDI. Major effects have been devloted to developing vaccines against TcdA and TcdB. How a fully ecctive vaccine should target all 3 toxins. CDT consists of an enzymatic component (CDTa) and a binding/translocation component (CDTb), the latter facilitating CDTa entry into host cells. CDTb contains two receptor-binding domains (RBD1 and RBD2), with RBD2 playing a critical role in host cell toxicity, making it a promising target for intervention.

In this study, we assessed the homology and immunogenicity of RBD2. Our in-silico analyses revealed that RBD2 is highly conserved across diverse toxinotypes and ribotypes. Immunization of mice and hamsters with RBD2 elicited robust IgG/A antibody responses against CDT. Notably, vaccinated mice were fully protected against lethal systemic CDT challenge, and hamsters were completely protected against a lethal oral spore challenge with the CDT-only C. difficile strain DSM101085. Furthermore, we demonstrated for the first time that CDT is lethal in both animal models, causing significant damage to the colon, cecum, and spleen—a previously unreported finding. Collectively, our data highlight RBD2 as a promising vaccine component for CDI prevention.

  • Open access
  • 32 Reads
Immunogenicity Study of Chimeric Secretory IgA: TB Multi-Epitopes Protein as Vaccine Candidate in Development of Mucosal Vaccine Against Tuberculosis

Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the most common infectious diseases worldwide. Considering that Mtb primarily infects the lungs, it may be more effective to match the route of infection to the route of vaccination when developing TB vaccines, in order to stimulate both systemic and mucosal immunity. This study explores the development and evaluation of a novel mucosal TB vaccine utilizing TB multi-epitopes.

Methods: The vaccine candidate was developed by engineering recombinant epitopes, including Ag85b, Acr, and RpfE, combined with SIgA. The constructs were cloned into AAV vectors. AAV vectors carrying the construct were co-transduced into mammary gland of goat, and milk was collected. The chimeric protein was purified from milk. BALB/c mice (n=5 per group) were divided into four main groups:PBS only, BCG+PBS, chimeric protein (Prot), and BCG with protein (BCG-Prot). The mice were immunized with 10 µg/ml chimeric protein intranasally, weekly, for three doses. After two weeks, the mice were sacrificed, and their splenocytes were cultured to evaluate their cellular responses. The IgG and IgA levels in serum, saliva, and lung lavage were measured using ELISA.

Results: Mice immunized with recombinant protein, especially those primed with BCG, showed higher IgG and IgA levels compared to other groups. With regard to cellular response, a significant increase in the percentage of activated CD4+ and CD8+ T-cells, memory cells, and cytokines production can be observed in BCG–protein group.

Conclusion: A protein complex formed by TB multi-epitopes and the secretory component can be expressed and purified in milk samples. Our study demonstrated that recombinant protein vaccine enhances mucosal immunity with intranasal immunization. The significant increase in humoral and cellular immune responses in mice, particularly in BCG-primed groups, highlights the potential of this vaccine as a booster candidate with BCG.

  • Open access
  • 9 Reads
Successive efficacy evaluation of various commercial live-attenuated avian coronavirus vaccination schedules against challenge with circulating field strain of genotype 23 lineage

Background

Infectious bronchitis virus (IBV) is a highly spreading, evolving virus that induces multiple manifestations, including respiratory, urinary, and reproductive symptoms, posing a significant threat to the local poultry industry. This study evaluated a variety of IBV vaccination regimens in broilers using commercially available live attenuated vaccines such as IB Primer, 793/B (4/91), IB-VAR2, and H120 against the local novel IBV-GI-23.3 strain.

Methods

The vaccines were administered to eight groups of SPF chicks either at 1 day age or at 1+14 days of age. The birds were then challenged with the NewValley-1-EGYIBV-GI23.3-2023 strain via the oculo-nasal route at 28 days post-vaccination, using 106 EID50/0.2 ml/chick. Ciliostasis activity and the scores for histopathological lesions were evaluated at 7days post-challenge (DPC). Virus shedding was monitored at 3, 5, and 7 DPC using the real-time RT-PCR method.

Results

The ciliostasis test indicated that the vaccinated groups receiving the IB Primer + 4/91 vaccine regime at 1 day age or at 1+14 days of age provided the highest levels of protection (65%, 68%). Similarly, administrating of IB Primer-VAR2 at 1+14 days of age demonstrated substantial protection (63%). Conversely, administering the H120+4/91 vaccination protocol at days 1 and 14 resulted in a moderate level of protection (53%). Tracheal IBV shedding quantification and subsequent assessment of trachea, proventriculus, bursa, and kidney degenerative changes were significantly lower in the vaccinated groups than in the control groups.

Conclusion

The heterologous combined IB Primer +4/91 program demonstrated the most significant protective efficacy against the IBV field challenge strains in broiler chickens compared to other vaccines.

  • Open access
  • 25 Reads
Novel Immunopeptidomic Insights into EHEC O157:H7 Immune Evasion in Cattle: Implications for Rational T-Cell-Based Vaccine Design
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Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes life-threatening disease in humans, characterized by bloody diarrhea and, in severe cases, brain and kidney damage. Ruminants—especially cattle—serve as the primary reservoir, where the bacterium asymptomatically colonizes the recto-anal junction. Our previous research demonstrated a mucosal immune bias towards a Th1 profile, with antigen-specific CD4⁺ and CD8⁺ T-cell proliferation. Mathematical modeling in humans suggests that EHEC O157:H7 effector proteins have evolved mechanisms to reduce MHC Class I (MHCI) ligand density, allowing the pathogen to escape immune surveillance through impaired antigen presentation and CD8⁺ T-cell recognition. In our study, we identified EHEC O157 peptides presented on infected bovine epithelial cells using peptide elution and mass spectrometry. The results revealed that most eluted peptides were derived from structural proteins with only one bacterial peptide—derived from the translocator effector protein EspF—but it did not meet the predicted binding threshold for the expressed MHCI alleles. Notably, two MHCI ligands originated from Intimin, a key bacterial adhesion factor crucial for cattle colonization, where one overlapped with a known CD4⁺ T-cell epitope, representing a promising vaccine candidate. Our in vitro model, using a bovine epithelial cell line expressing BoLA-1*023:01 and autologous CD8⁺ T cells, showed that EHEC O157 suppresses antigen-specific CD8⁺ T-cell activation, suggesting that the bacterial-secreted effector interferes with peptide processing and/or MHCI loading. This study provides a novel insight into veterinary immunology, particularly in the context of extracellular pathogens. It highlights the importance of including both CD4⁺ and CD8⁺ T epitopes in rational vaccine design—an often underexplored strategy for extracellular pathogens like EHEC O157. By integrating immunopeptidomics, in silico prediction, and a bovine in vitro model, we establish a basis for next-generation vaccines to eliminate persistent infections and limit zoonotic transmission.

  • Open access
  • 46 Reads
Adverse events of mRNA vaccine: mechanisms, risks and management
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Introduction: mRNA vaccines have been pivotal in combating COVID-19, yet their deployment is associated with reports of adverse events (AEs). A better understanding and study of adverse reactions can promote the advancement of vaccine technology. Therefore, this study comprehensively characterizes these AEs, elucidates underlying mechanisms, and proposes management strategies to advance vaccine safety.

Methods: A systematic literature search was conducted across ScienceDirect, PubMed, SpringerLink, and Web of Science from January 2019 to April 2025, using the search terms "mRNA vaccine adverse" in the title, abstract, and keywords. Global pharmacovigilance databases, including EudraVigilance, VAERS, and CANVA, were also included. After deduplication and relevance analysis of the literature, the required documents were obtained, based on whom AEs were classified according to anatomical systems and mechanisms. Finally, visual analysis was conducted to complete the study.

Results: According to the method above, 87 articles, comprising clinical trials and case reports, met the inclusion criteria, following the PRISMA workflow referring to academic standard. AEs were categorized by anatomical systems and mechanistic axes. Anatomically, AEs are classified into four categories: cardiovascular AEs, neurological AEs, inflammatory AEs and mucocutaneous disorders. Cardiovascular AEs included myocarditis, thrombosis, and systemic capillary leak syndrome. Neurological AEs encompassed headaches, acute transverse myelitis, Bell’s palsy, and delirium. Mucocutaneous disorders featured urticaria, vitiligo, and oral ulcers. Inflammatory AEs involved IgA nephropathy, subacute thyroiditis, rhabdomyolysis, and autoimmune flares like SLE, RA. Mechanistically, AEs were categorized into three axes: host susceptibility, delivery system interactions, mRNA component immunogenicity.

Conclusions: mRNA vaccine AEs arise from complex interactions between host biology, delivery systems, and mRNA immunogenicity. Key strategies for mitigation include: nucleotide chemistry refinement like pseudouridine modification, codon optimization, tissue-targeted LNPs, tunable adjuvants, and biomarker-guided risk stratification. Future research must prioritize mechanistic insights into molecular mimicry and host-specific vulnerabilities to enable safer, precision-engineered mRNA platforms.

  • Open access
  • 23 Reads
Single-cell immune profiling reveals potent anti-tumor immune response in virus-like particle vaccine and anti-CTLA4 treatment through lymphatic delivery

Introduction:
Immune checkpoint inhibitors such as anti-CTLA-4 enhance anti-tumor immunity but are often limited by immune-related adverse events (irAEs) caused by non-specific T cell activation. Virus-like particles (VLPs) presenting tumor antigens offer a strategy to selectively prime tumor-specific T cells, potentially enhancing therapeutic efficacy while minimizing off-target toxicity.

Methods:
We investigated a lymphatic-targeted immunotherapy approach in a B16F10 melanoma mouse model. Mice received VLPs carrying the tumor-associated antigen PMEL via intradermal vaccination to a non-tumor-draining lymph node (non-tdLN), followed by αCTLA-4 checkpoint blockade delivered either systemically (intravenous) or regionally (intradermally to the same non-tdLN). Single-cell RNA and TCR sequencing were used to characterize immune cell phenotypes and T cell clonal dynamics in the tumor microenvironment. Functional assays and histopathological analysis assessed tumor-specific activity and irAE profiles.

Results:
Regional αCTLA-4 delivery synergized with VLP vaccination to promote infiltration and clonal expansion of non-exhausted CD8⁺ effector and CD4⁺ Th1 T cells while reducing regulatory T cells. VLPs alone induced PMEL-specific CD8⁺ T cells, and regional αCTLA-4 further amplified this response. Functional assays confirmed increased tumor-specific T cell activation with minimal bystander T cell infiltration into normal tissues. Additionally, αCTLA-4 promoted macrophage activation, upregulating interferon signaling and T cell costimulation pathways.

Conclusions:
Lymphatic-targeted combination therapy with VLP vaccination and regional αCTLA-4 delivery drives potent, tumor-specific immune responses while minimizing systemic toxicity. This approach offers a promising strategy to improve the efficacy and safety of cancer immunotherapy.

  • Open access
  • 22 Reads
Next-Generation Cancer Vaccines and Immunotherapy: Neo-Antigen Strategies and AI-Driven Personalization for Precision Tumor Targeting

Cancer immunotherapy has revolutionized oncology by using the immune system to combat cancer, with next-generation vaccines emerging as a transformative approach. The use of neo-antigens derived from tumor-specific mutations has significantly improved vaccine precision, enabling targeted immune activation against heterogeneous tumors. Furthermore, artificial intelligence (AI) is revolutionizing vaccine design by predicting the optimal antigen selection, optimizing immune epitopes, and personalizing therapies for each patient. We review recent advancements in cancer vaccine strategies, particularly neo-antigen-based and AI-driven personalized approaches to enhancing tumor-specific immune responses. The evolution of vaccine platforms, including dendritic cell vaccines, mRNA vaccines, and viral vector-based approaches, is highlighted with a focus on their mechanisms in generating strong antitumor immunity. These platforms not only differ in delivery efficiency and antigen expression but also offer unique immunological advantages. Combination strategies such as vaccines with immune checkpoint inhibitors, adoptive cell therapies (CAR-T, TCR-T), and tumor-infiltrating lymphocyte (TIL) therapy demonstrate synergistic effects in overcoming immune evasion and improving clinical outcomes. Despite these advancements, challenges such as tumor immunosuppression, antigen escape, and manufacturing scalability remain. Future directions highlight multi-omics integration, nanotechnology-based delivery systems, and biomarker-driven personalization to refine vaccine efficacy. The convergence of immunology, bioinformatics, and clinical oncology is essential to bring these innovations into routine clinical practice, enabling next-generation immunotherapies that maximize tumor eradication and long-term survival.

  • Open access
  • 10 Reads
Selection, Design and Immunogenicity Studies of ASFV Antigens for Subunit mRNA Cocktail Vaccines with Specific Immune Response Profiles
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The outbreaks African swine fever (ASF) in Eurasia have caused tremendous economic losses and the incursion to US would be disastrous to swine industry. Safe and effective vaccines have not been developed so far. Here, we report a novel ASFV mRNA vaccine designed with multiple rationalities to induce robust humoral and cellular immunities. Candidate vaccine antigens are selected by referring to homologs of protective antigens from the closely related vaccinia virus, known antigens eliciting strong host immune response, and viral capsid engineering for membrane-anchoring for optimal B cell engagement. To specifically induce strong T cell response, a T cell-directed vaccine antigen is designed by fusing multiple T cell epitopes (MTE) that are experimentally determined previously or predicted MHC-I high binders. Candidate antigens are formulated into lipid nanoparticle (LNP)- mRNA and further immunogenicity assessment in both mice and pigs reveals that different antigens elicits very distinct immune profiles including total antibody response, antibody effector functionality, and T cell response. Notably, the T cell-directed antigen induced robust cellular immunity. Furthermore, we demonstrated that multiple candidate cocktail vaccines based on distinct antigen immune profiles induced robust B cell and T cell immunities. Overall, The novel-designed vaccines coupled with mRNA technology shed light for an effective vaccine development against ASFV and strategies reported here can be utilized for developing vaccines against other large complex DNA viruses, such as monkeypox virus.

  • Open access
  • 16 Reads
Preclinical Potential of γδ T Cells in Novel Personalized Antigen-Directed Immunotherapy for Triple-Negative Breast Cancer

Introduction: Triple-negative breast cancer (TNBC) is highly aggressive, with poor prognosis and limited effective treatments. Virus-like particles (VLPs)-based personalized vaccines offer a promising way to induce lasting antitumor immunity. While γδ T cells play roles in cancer, their interaction with nanoparticles is unclear. Administration route impacts efficacy: subcutaneous (s.c.) delivery within lymphatic watersheds targeting draining lymph nodes (dLNs), enhance local and systemic immune responses. Method: We developed plant-derived VLPs carrying TLR ligands and validated them by cryo-EM and biochemical assays. Using imaging flow cytometry and in vivo studies in the 4T1 s.c. TNBC model, we examined γδ T cell–VLP interaction and their role in vaccine efficacy. We compared three s.c. routes: systemic, targeting tdLNs, and targeting non-tdLNs. Survival was assessed under different dosing and ICI co-treatment. CD4+, CD8+, and γδ T cells were depleted to determine their contributions. Results: γδ T cells were expanded in dLNs and internalized VLPs post-vaccination. γδ subsets showed distinct activation. tdLN-targeted delivery, especially with ICI, gave the best outcomes. Depletion of CD4+, CD8+, or γδ T cells impaired efficacy, showing all are essential. Despite their rarity, γδ T cells were key to early tumor control. Conclusion: Our study highlights a crucial early role for γδ T cells in VLP-based cancer vaccination. Efficacy improved with ICI co-treatment and tdLN-targeted delivery, supporting inclusion of rare immune subsets like γδ T cells in cancer immunotherapy.

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