Search Results (229)

Influenza viruses continue to undergo antigenic drift and shift, resulting in the need to update existing vaccines annually. Therefore, the development of a universal influenza vaccine has become an urgent global need. This paper reviews the functions of common antigenic targets of influenza vaccines and their advantages and disadvantages in universal vaccine design. We also summarize the common design strategies for universal influenza vaccines, which mainly include the immunofocusing strategy, multi-target combination strategy, T-cell strategy, computationally optimized broadly cross-reactive antigenic strategy (COBRA), and artificial intelligence strategy. In addition, we also sort out the latest research progress of universal influenza vaccines under different technological routes. This will help researchers better grasp the latest developments of universal influenza vaccines. Full article

Background: COVID-19 vaccination has been a key tool in protecting healthcare workers (HCWs), but breakthrough infections have occurred. The durability of vaccine-induced immunity and its impact on HCWs remain critical for public health strategies. Methods: In this small cohort study (n = 32), we assessed antibody levels and breakthrough infection rates in HCWs over 12 months post-vaccination, providing insights for booster strategies and infection control. A cohort of 32 HCWs was screened for SARS-CoV-2 infection using weekly self-administered swabs and blood samples collected at baseline, 6 months, and 12 months. SARS-CoV-2 antibodies (IgG, IgM) targeting spike proteins and nucleocapsids were analyzed using a multi-antigen serology panel. Pooled nucleic acid testing was employed for infection detection. Results: Nine participants showed breakthrough infections, with nucleocapsid antibodies indicating prior infection. Eight of these cases occurred after the third vaccine dose during the Omicron-dominant period. Anti-spike antibody levels declined significantly in participants without prior infection, while those with breakthrough infections exhibited increased levels. The half-life of S1 and S1 receptor-binding domain (RDB) vaccine-induced antibodies was 144 and 166 days, respectively, which aligns with CDC data. These findings provide valuable insights for determining the optimal timing of booster doses. Conclusions: Our findings highlight the waning antibody levels over time and the occurrence of breakthrough infections. Although based on a small sample, these data support the need for ongoing monitoring and timely boosters. Full article

Monkeypox virus (MPXV) has caused 148,892 confirmed cases and 341 deaths from 137 countries worldwide, as reported by the World Health Organization (WHO), highlighting the urgent need for effective vaccines to prevent the spread of MPXV. Traditional vaccine development is low-throughput, expensive, time consuming, and susceptible to reversion to virulence. Alternatively, a reverse vaccinology approach offers a rapid, efficient, and safer alternative for MPXV vaccine design. Here, MPXV proteins associated with viral infection were analyzed for immunogenic epitopes to design multi-epitope vaccines based on B-cell, CD4+, and CD8+ epitopes. Epitopes were selected based on allergenicity, antigenicity, and toxicity parameters. The prioritized epitopes were then combined via peptide linkers and N-terminally fused to various protein adjuvants, including PADRE, beta-defensin 3, 50S ribosomal protein L7/12, RS-09, and the cholera toxin B subunit (CTB). All vaccine constructs were computationally validated for physicochemical properties, antigenicity, allergenicity, safety, solubility, and structural stability. The three-dimensional structure of the selected construct was also predicted. Moreover, molecular docking and molecular dynamics (MD) simulations between the vaccine and the TLR-4 immune receptor demonstrated a strong and stable interaction. The vaccine construct was codon-optimized for high expression in the E. coli and was finally cloned in silico into the pET21a (+) vector. Collectively, these results could represent innovative tools for vaccine formulation against MPXV and be transformative for other infectious diseases. Full article

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

Fasciola gigantica (F. gigantica) is a vital parasite that causes fasciolosis. Liver fluke infections affect livestock animals, and the Fasciola species (Fasciola spp.) vaccine has been tested for many types of these diseases. Currently, computer-based vaccine design represents an attractive alternative for constructing vaccines. Thus, this study aimed to design the epitopes of linear B-cells (BCL) and helper T lymphocytes (HTL) using an immunoinformatic approach and to investigate in silico and the mice’s immune response. A non-conserved host region, overlapping F. gigantica cathepsin B proteins (FgCatB), and the highest conserved residue percentages were the criteria used to construct epitopes. The GPGPG linker was used to link epitopes in the multi-epitope Fasciola gigantica cathepsin B (MeFgCatB) peptide. The MeFgCatB peptide has high antigenicity, non-allergenicity, non-toxicity, good solubility, and a high-quality structure. The molecular docking between the MeFgCatB peptide and Toll-like receptor 2 (TLR-2) was evaluated. The IgM, IgG1, and IgG2 levels were elevated in silico. In mice, the MeFgCatB peptide was synthesized and administered as an injection. The MeFgCatB-specific IgG1 and IgG2a levels were elevated after week 2, showing a predominance of IgG1. The rFgCatB1, rFgCatB2, and rFgCatB3 were detected using the MeFgCatB peptide-immunized sera. The MeFgCatB peptide-immunized sera were detected at approximately 28–34 kDa in the whole body. In addition, the MeFgCatB immunized sera can positively signal at the caecal epithelium in the NEJ, 4WKJ, and adult stages. In summary, the MeFgCatB peptide is able to induce mixed Th1/Th2 immune responses with Th2 dominating and to detect the native protein of F. gigantica. The MeFgCatB peptide should help against F. gigantica in future experiments. Full article

Group A Streptococcus (GAS) imposes a significant global health burden across all age groups, annually causing over 600 million cases of pharyngitis and more than 18 million severe invasive infections or sequelae. The resurgence of scarlet fever globally and streptococcal toxic shock syndrome (STSS) outbreaks in Japan have brought GAS infections back into the spotlight as a pressing global health concern. Unfortunately, no licensed vaccine against GAS is yet available for clinical use. Our comprehensive review examines the developmental history of GAS vaccines, outlining the research trajectory from early inactivated vaccines to contemporary multivalent, conjugate, multi-antigen, and mRNA-based vaccine platforms. It systematically analyzes clinical trial outcomes of GAS vaccines, highlighting recent advances in both M protein-based and non-M protein vaccine candidates while summarizing promising target antigens. The review concludes with critical strategies to accelerate vaccine commercialization, including enhanced investment in research and development, expanded collaborations, leveraging advanced vaccine technologies, streamlined clinical trials, and strengthened public health advocacy. This review critically evaluates the current evidence and future prospects in GAS vaccine development, emphasizing innovative strategies and engaging broader stakeholders to accelerate GAS vaccine development. Full article

Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides (LeishPts) encapsulated in doubly adjuvanted self-nanoemulsifying drug delivery systems (ST-SNEDDSs), this study aims to assess ST-SNEDDS-based nanoemulsions as vehicles for the delivery of antigenic proteins. Methods: Model antigens (e.g., BSA-FITC, OVA) were encapsulated in ST-SNEDDS after being complexed with the cationic phospholipid dimyristoyl phosphatidylglycerol (DMPG) via hydrophobic ion pairing. The nanoemulsions were characterized with respect to droplet diameter, zeta potential, stability, protein loading, protein release from the nanodroplets in different release media and cell uptake. Results: Both model antigens exhibited high encapsulation efficiency (>95%) and their release from the nanodroplets was shown to be strongly affected by the type of release medium (e.g., PBS, FBS 10% v/v) and the ratio of its volume to that of the oily phase, in agreement with predictions of protein release. Protein-loaded nanoemulsion droplets labeled with Cy-5 were found to be efficiently taken up by macrophages (J774A.1) in vitro. However, no colocalization of the labeled nanodroplets and BSA-FITC could be observed. Conclusions: It was revealed that in contrast with LeishPts, whole protein molecules may not be appropriate antigenic cargo for ST-SNEDDS formulations due to the rapid protein release from the nanodroplets in release media simulating in vitro culture and in vivo conditions such as FBS 10% v/v. Full article

In the current global health environment, the spread of the monkeypox virus (MPXV) and the persistent threat of human immunodeficiency virus (HIV) have become critical public health challenges. Since 2022, MPXV has rapidly disseminated worldwide, and nearly half of MPXV-infected individuals are co-infected with HIV. This complex situation calls for innovative preventive strategies. In this study, an innovative multi-epitope vaccine was designed using bioinformatics and immunoinformatic approaches. Ten HIV proteins and nine MPXV proteins were used to predict potential epitopes. Non-allergenic, highly antigenic, IFN-γ-inducible, and non-toxic epitopes were selected to construct the multi-epitope vaccine. It was found that the designed vaccine construct was highly antigenic, soluble, and had acceptable physicochemical properties. Based on molecular docking and molecular dynamics simulation (MDs) analyses, the vaccine construct demonstrated stable and robust interactions with Toll-like receptors (TLR2, TLR3, and TLR4). Although no actual animal experiments have been conducted to evaluate the vaccine’s effectiveness, immune simulations showed that the vaccine could elicit potent humoral and cell-mediated immune responses. Overall, this study provides a promising vaccine candidate against MPXV and HIV co-infection and emphasizes innovative strategies to interrupt the international transmission of these two viruses. Full article

Background/Objectives: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine design. Methods: Here we developed a trivalent mRNA vaccine encoding the domains I-II of envelope glycoprotein E2 from three BVDV genotypes (3E2), introduced with bovine IgG1 Fc (bFc), STABILON (hStab), and artificial virus-like particle (ARVLP) containing CD80 transmembrane (TM) domain, FcγRII cytoplasmic domain, and WW domain of ITCH. Then, in vitro expression, in vivo immunogenicity and neutralizing antibody analysis were performed to evaluate the vaccines. Results: The in vitro expression results showed that bFc and hStab dramatically enhanced antigen expression and immunogenicity. In addition, the ARVLP further enhanced the secretion and potency of neutralizing antibodies. Finally, the immunogenicity of the bFc_BVDV_3E2_ARVLP_hStab mRNA vaccine was evaluated in mice, guinea pigs, and lactating goats and high levels of neutralizing antibodies against all three BVDV genotypes were detected. Conclusions: Our trivalent design strategy with bFc, hStab, and ARVLP shows highly efficient expression as well as strong immunogenicity and provides a promising approach for next-generation BVDV vaccines with broader and stronger protection. Full article

Infectious laryngotracheitis (ILT) is a severe upper respiratory disease highly contagious in chickens that causes a huge economic impact on the poultry industry all over the world. The current study aimed to design a multi-epitope-based vaccine candidate using envelope glycoprotein B and glycoprotein D of the ILT virus using an immune informatics approach. The glycoproteins B and D are crucial for attachment as well as entry of ILT virus inside the cell, which makes them a potential option for designing vaccine candidates. The prediction of epitopes, viz. helper T lymphocyte, cytotoxic T lymphocyte and interferon-gamma producing epitopes, was performed and high-scoring predicted epitopes were joined in an organized manner using suitable linkers to design the final vaccine candidate. The avian beta-defensin 1 was included as an adjuvant in the amino-terminal of the vaccine design that possesses antimicrobial activity and histidine residues at the carboxy-terminal for the purpose of purification. The final vaccine candidate was evaluated for its physicochemical characteristics, solubility, antigenicity, stability, and allergenicity and validated for its modeling. Molecular docking, binding affinity, and interacting residues between the vaccine candidate and immune receptors, viz. TLR 3, MHC Class I and Class II were assessed. Further, to assess the immune response profile generated by the final vaccine design, an insilico immune simulation study was also performed. The findings of this study revealed that the final vaccine candidate was antigenic, nonallergenic, stable, interacted with immune receptors, and able to produce antibodies as well as cellular immune responses against ILTV infection. Full article

Background: Immunization coverage in Nigeria is low, with many children missing out on important lifesaving vaccines. To enable a better understanding of contextual factors towards increasing uptake, we piloted a Decentralized Immunization Monitoring (DIM) approach in the Kumbotso local government area (LGA) of Kano state, Nigeria, to identify wards with low vaccination rates and understand why this is happening. The findings were used to improve routine immunization (RI) programs and reduce the number of unvaccinated children and children yet to receive their first dose of diphtheria–pertussis–tetanus (DPT) vaccine, referred to as Zero-Dose children (ZD). Methods: This study adopted a cross-sectional design approach using the Behavioural and Social Drivers of Vaccination (BeSD) framework and the Lot Quality Assurance Sampling (LQAS). The study population comprised caregivers of children aged 0–11 months and 12–23 months across the 11 wards in Kumbotso District, Kano State, Nigeria, using a segmentation sampling approach. The study covered 209 settlements selected using probability proportionate to size (PPS) sampling from the wards. Univariate and bivariate analyses were performed to show patterns and relations across variables. Results: Out of 418 caregivers surveyed, 98.1% were female. Delayed vaccination was experienced by 21.9% of children aged 4.5–11 months, while the prevalence of ZD was estimated at 26.8% amongst the older cohort (12–23 months). A total of 71.4% of the delayed group and 89.1% of the ZD group remained unvaccinated. Caregiver education, rural residence, and home births correlated with delayed/ZD status (p < 0.05). Logistic regression associated higher caregiver education with reduced delayed vaccination odds (OR:0.34, p < 0.001) and urban residence with lower ZD odds (OR:1.89, p = 0.036). The antigen coverages of BCG (81.5%), DPT3 (63.6%), and measles 1 (59.7%) all surpassed the national dropout thresholds. Kumbotso, Unguwar Rimi, and Kureken Sani wards were all identified as underperforming and therefore targeted for intervention. Negative vaccine perceptions (50% delayed, 53.6% ZD) and distrust in health workers (46.4% delayed, 48.2% ZD) were significant barriers, though the caregiver intent to vaccinate was protective (OR: 0.27, p < 0.001). The cost of accessing immunization services appeared to have a minor effect on coverage, as the majority of caregivers of delayed and ZD children reported spending less than 200 Naira (equivalent to USD 0.15) on transport. Conclusions: This pilot study highlighted the utility of LQAS and BeSD in identifying low-performing wards, barriers, and routine immunization gaps. Barriers included low caregiver education, rural residence, and negative vaccine perceptions/safety. Caregiver education and urban residence were protective factors against delayed and ZD vaccination, suggesting social and systemic barriers, particularly in rural and less educated populations. Antigen-specific coverage showed disparities, with dropouts for multi-dose vaccines exceeding the national thresholds of 10%. Targeted measures addressing education, trust, and systemic issues are needed. Findings emphasize decentralized monitoring, community engagement, and context-specific strategies to reduce ZD children and ensure equitable vaccination in Nigeria. Full article

Natural autoantibodies (nAAbs) recognize self-antigens and are an important component of the immune system, having evolved from invertebrates to vertebrates, and are viewed as stable byproducts of immune function and essential players in health and disease. Initially characterized by their conserved nature and multi-reactivity, primarily as IgM isotypes, nAAbs are now recognized for their adaptability in response to infections and vaccinations, bridging innate and adaptive immunity. The nAAbs and the cellular elements, such as γδ T, iNKT, and MAIT cells, of the natural immune system perform a primary defense network with moderate antigen-specificity. This comprehensive literature review was conducted to analyze the role of natural autoantibodies (nAAbs) in health and disease. The review focused on research published over the past 40 years, emphasizing studies related to infectious diseases, vaccinations, and autoimmune disorders. Recent studies suggest that nAAbs engage in complex interactions in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and type 1 diabetes. Their roles in immunological processes, such as maternal tolerance during pregnancy, further underscore their complexity. Emerging evidence indicates that nAAbs and the cellular elements of the natural immune system may contribute to both disease pathogenesis and protective mechanisms, highlighting their dual nature. Continued research on nAAbs is vital for improving our understanding of immune responses and developing therapeutic strategies for autoimmune disorders and infectious diseases. Full article

The emergence of complex and rapidly evolving pathogens necessitates innovative vaccine platforms that move beyond traditional methods. This review explores the transformative potential of next-generation vaccine technologies, focusing on the combined use of synthetic biology, nanotechnology, and systems immunology. Synthetic biology provides modular tools for designing antigenic components with improved immunogenicity, as seen in mRNA, DNA, and peptide-based platforms featuring codon optimization and self-amplifying constructs. At the same time, nanotechnology enables precise antigen delivery and controlled immune activation through engineered nanoparticles such as lipid-based carriers, virus-like particles, and polymeric systems to improve stability, targeting, and dose efficiency. Systems immunology aids these advancements by analyzing immune responses through multi-omics data and computational modeling, which assists in antigen selection, immune profiling, and adjuvant optimization. This approach enhances both humoral and cellular immunity, solving challenges like antigen presentation, response durability, and vaccine personalization. Case studies on SARS-CoV-2, Epstein–Barr virus, and Mycobacterium tuberculosis highlight the practical application of these platforms. Despite promising progress, challenges include scalability, safety evaluation, and ethical concerns with data-driven vaccine designs. Ongoing interdisciplinary collaboration is crucial to fully develop these technologies for strong, adaptable, globally accessible vaccines. This review emphasizes next-generation vaccines as foundational for future immunoprophylaxis, especially against emerging infectious diseases and cancer immunotherapy. Full article

The rapid expansion of aquaculture is vital for global food security, yet it faces persistent threats from disease outbreaks, vaccine inefficacy, and antibiotic overuse, all of which undermine sustainability. Conventional vaccines often fail to induce robust mucosal immunity, spurring interest in probiotics as adjuvants to enhance immunogenicity. Probiotics such as Bacillus subtilis and Lactobacillus casei modulate fish microbiomes, fortify mucosal barriers, and activate innate immune responses via mechanisms including Toll-like receptor signaling and cytokine production. These actions prime the host environment for prolonged adaptive immunity, improving antigen uptake and pathogen clearance. Experimental advances—such as Bacillus subtilis-engineered spores increasing survival rates to 86% in Vibrio anguillarum-challenged European seabass—demonstrate the potential of this synergy. Innovations in delivery systems, including chitosan–alginate microcapsules and synbiotic formulations, further address oral vaccine degradation, enhancing practicality. Probiotics also suppress pathogens while enriching beneficial gut taxa, amplifying mucosal IgA and systemic IgM responses. However, challenges such as strain-specific variability, environmental dependencies, and unresolved ecological risks persist. Optimizing host-specific probiotics and advancing multi-omics research is critical to unlocking this synergy fully. Integrating probiotic mechanisms with vaccine design offers a pathway toward antibiotic-free aquaculture, aligning with One Health principles. Realizing this vision demands interdisciplinary collaboration to standardize protocols, validate field efficacy, and align policies with ecological sustainability. Probiotic–vaccine strategies represent not merely a scientific advance but an essential evolution for resilient, ecologically balanced aquaculture systems. Full article

Background: Yiqi Zengmian (YQZM) functions as an immunopotentiator by enhancing both cellular and humoral immunity. However, its pharmacodynamic active constituents, particularly those absorbed into the bloodstream, and mechanism of action remain unclear. This study aimed to investigate the immunopotentiating effects and mechanisms of YQZM in mice immunized with the BBIBP-CorV (Beijing Bio-Institute of Biological Products Coronavirus Vaccine). Methods: Serum pharmacochemistry and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) were employed to identify bioavailable components of YQZM. The mice received the BBIBP-CorV twice on days 1 and 14, while YQZM was orally administered for 28 days. Neutralization assays and ELISA quantified antigen-specific antibodies (abs), flow cytometry (FC) and intracellular cytokine staining (ICS) were used to assess immune cell populations and their cytokines, and an enzyme-linked immunospot assay (ELISpot) quantified memory T and B cells (MBs and MTs). To identify underlying mechanisms, network pharmacology, RNA sequencing (RNA-Seq), molecular docking, Western blotting (WB), and quantitative reverse transcription PCR (RT-qPCR) were performed. Results: YQZM significantly enhanced antigen-specific antibody titers, immune cell proportions, cytokine levels, and memory lymphocyte functions. UPLC-MS/MS analysis identified 31 bioactive compounds in YQZM. KEGG enrichment analysis based on RNA-Seq and network pharmacology implicated the TLR-JAK-STAT signaling pathway in YQZM’s immune-enhancing effects. WB and RT-PCR validated that YQZM upregulated the expression of critical nodes in the TLR-JAK-STAT signaling pathway. Furthermore, molecular docking indicated that YQZM’s primary active components exhibited strong binding affinity for critical proteins. Conclusions: YQZM effectively enhances vaccine-induced innate and adaptive immunity via a multi-component, multi-target mechanism, among which the TLR-JAK-STAT signaling pathway is a validated molecular target. Full article