Potential Vaccine Research Articles

A comprehensive investigation of Glycoprotein-based nucleic acid vaccines for Hantaan Virus

Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, naked DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering comparable in vivo protective efficacy to the inactivated vaccines. Notably, compared to the inactivated vaccine, mRNA vaccine induced stronger virus-specific T-helper 1 cell immune response, while DNA-LNP elicited higher levels of neutralizing antibodies in mice. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines.

Designing novel multiepitope mRNA vaccine targeting Hendra virus (HeV): An integrative approach utilizing immunoinformatics, reverse vaccinology, and molecular dynamics simulation.

Human and animal health is threatened by Hendra virus (HeV), which has few treatments. This in-silico vaccine design study focuses on HeV G (glycoprotein), F (fusion protein), and M (matrix protein). These proteins were computationally assessed for B and T-cell epitopes after considering HeV strain conservation, immunogenicity, and antigenicity. To improve vaccination immunogenicity, these epitopes were selectively ligated into a multiepitope construct. To improve vaccination longevity and immunological response, adjuvants and linkers were ligated. G, F, and M epitopes were used to create an mRNA HeV vaccine. Cytotoxic, helper, and linear B-lymphocytes' epitopes are targeted by this vaccine. The population coverage analysis demonstrates that multi-epitope vaccination covers 91.81 percent of CTL and 98.55 percent of HTL epitopes worldwide. GRAVY evaluated the vaccine's well-characterized physicochemical properties -0.503, indicating solubility and functional stability. Structure analysis showed well-stabilized 2° and 3° structures in the vaccine, with alpha helix, beta sheet, and coil structures (Ramachandran score of 88.5% and Z score of -3.44). There was a strong affinity as shown by docking tests with TLR-4 (central score of -1139.4 KJ/mol) and TLR-2 (center score of -1277.9 KJ/mol). The coupled V-apo, V-TLR2, and V-TLR4 complexes were tested for binding using molecular dynamics simulation where extremely stable complexes were found. The predicted mRNA structures provided significant stability. Codon optimization for Escherichia. coli synthesis allowed the vaccine to attain a GC content of 46.83% and a CAI score of 1.0, which supports its significant expression. Immunological simulations indicated vaccine-induced innate and adaptive immune reactions. Finally, this potential HeV vaccine needs more studies to prove its efficacy and safety.

Identification and characterization of linear B-cell epitopes on African swine fever virus H171R protein.

African swine fever virus (ASFV) poses a severe threat to the global swine industry. This study characterizes linear B-cell epitopes on the crucial ASFV H171R protein, facilitating the development of improved diagnostics and subunit vaccines. Four immunogenic epitopes were identified, offering valuable information for designing sensitive diagnostic assays and potential subunit vaccine candidates. By advancing the understanding of H171R's antigenic landscape, this research contributes to controlling ASFV's devastating impacts, safeguarding the swine industry, and ensuring food security.

Neoantigen-Based Cancer Vaccines: Current Innovations, Challenges, And Future Directions In Personalized Immunotherapy

The development of neoantigen-based cancer vaccines represents a breakthrough in personalized immunotherapy due to their ability to elicit strong and effective tumor-specific immune responses. Unlike conventional cancer vaccines, neoantigen vaccines target mutations found explicitly in tumor cells, thus maximizing specificity and minimizing immune tolerance. The review explores the current status of neoantigen vaccines and their mechanisms, development, and clinical applications. In contrast, it also explores the challenges of personalized vaccines, such as identifying neoantigens and their manufacturing, along with biological factors and regulatory hurdles. Future innovations and strategies are discussed to overcome resistance and relapse. Critical issues like global access, equity, and scalability must be addressed for its more comprehensive imple-mentation. This review article discusses the potential of neoantigen vaccines in cancer therapy, detailing ongoing research and clinical trials, while addressing the persistent challenges that must not be underestimated.

Predictive immunoinformatics reveal promising safety and anti-onchocerciasis protective immune response profiles to vaccine candidates (Ov-RAL-2 and Ov-103) in anticipation of phase I clinical trials.

Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025. Notably, Ov-RAL-2 and Ov-103 antigens have shown great promise during pre-clinical development, however, the overall success rate of vaccine candidates during clinical development remains relatively low due to certain adverse effects and immunogenic limitations. This study, thus, aimed at predicting the safety and immunogenicity of Ov-RAL-2 and Ov-103 potential onchocerciasis vaccine candidates prior to clinical trials. Advanced molecular simulation models and analytical immunoinformatics algorithms were applied to predict potential adverse side effects and efficacy of these antigens in humans. The analyses revealed that both Ov-RAL-2 and Ov-103 demonstrate favourable safety profiles as toxicogenic and allergenic epitopes were found to be absent within each antigen. Also, both antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes (antibodies, cytokines, and T- Cell epitopes) associated with protective immunity against onchocerciasis. In agreement, virtual vaccination simulation forecasted heightened, but sustained levels of primary and secondary protective immune responses to both vaccine candidates over time. Ov-103 was predicted to be non-camouflageable, as it lacked epitopes identical to protein sequences in the human proteome. Indeed, both antigens were able to bind with high affinity and activate the innate immune TLR4 receptor, implying efficient immune recognition. These findings suggest that Ov-RAL-2 and Ov-103 can induce sufficient protective responses through diverse humoral and cellular mechanisms. Overall, our study provides additional layer of evidence for advancing the clinical development of both vaccine candidates against onchocerciasis.

Factors affecting human papillomavirus vaccine acceptance among parents of Primary 4 to 6 boys and girls in Hong Kong.

Human papillomavirus (HPV) poses a substantial but underestimated healthcare burden in Hong Kong. This study investigated factors affecting parental acceptance of HPV vaccination after the introduction of an immunisation programme for primary school girls. We assessed parental perceptions and related factors concerning HPV vaccination for both boys and girls. We conducted a cross-sectional survey between December 2021 and February 2022 among parents of Primary 4 to 6 students in Hong Kong. Our self-administered online survey collected data regarding socio-demographic characteristics, awareness and knowledge of HPV vaccination, attitudes towards HPV vaccination, and acceptance of HPV vaccination. Characteristics were compared between boys' parents and girls' parents. Factors associated with vaccine acceptance were analysed by multivariate logistic regression. We observed high awareness of HPV vaccination among boys' parents and girls' parents; however, they demonstrated relatively poor knowledge of HPV and the HPV vaccine. An alarming low HPV vaccination uptake rate was also observed. Attitudes towards the HPV vaccine were similar between parent groups. A majority of parents believed that the HPV vaccine was safe and effective in preventing infection. Parents of boys showed lower HPV vaccine acceptance. Factors associated with acceptance differed between parent groups. High awareness of HPV and HPV vaccine is predictive of vaccine acceptance. Boys' parents are less likely to accept HPV vaccination and emphasis should be placed on addressing potential HPV vaccine hesitancy in this group. Public education should also aim to raise awareness of government vaccination programme, and implementation of catch-up vaccination programme to school children beyond primary school should be considered.

Insights into Genetic and Antigenic Characteristics of Influenza A(H1N1)pdm09 Viruses Circulating in Sicily During the Surveillance Season 2023-2024: The Potential Effect on the Seasonal Vaccine Effectiveness.

After disruption in the influenza circulation due to the emergence of SARS-CoV-2, the intensity of seasonal outbreaks has returned to the pre-pandemic levels. This study aimed to evaluate the evolution and variability of whole-genome sequences of A(H1N1)pdm09, the predominant influenza virus in Sicily (Italy) during the season 2023-2024. The potential vaccine efficacy was calculated using the pepitope model based on amino acid changes in the dominant epitope of hemagglutinin. The HA gene sequences showed several amino acid substitutions, some of which were within the major antigenic sites. The phylogenetic analysis showed that Sicilian strains grouped into two main genetic clades (6B.1A.5a.2a.1 and 6B.1A.5a.2a) and several subclades. Notably, about 40% of sequences partially drifted from the WHO-recommended vaccine strain A/Victoria/4897/2022 for the Northern Hemisphere. These sequences mostly belonged to the subclades C.1.8 and C.1.9 and harboured the amino acid mutations responsible for the modest predicted vaccine efficacy (E = 38.12% of 53%, pepitope = 0) against these viruses. Amino acid substitutions in other gene segments were also found. Since influenza viruses are constantly evolving, genomic surveillance is crucial in monitoring their molecular evolution and the occurrence of genetic and antigenic changes, and, thus, their potential impact on vaccine efficacy.

Mixed Th1/Th2/Th17 Responses Induced by Plant Oil Adjuvant-Based B. bronchiseptica Vaccine in Mice, with Mechanisms Unraveled by RNA-Seq, 16S rRNA and Metabolomics.

The current Bordetella bronchiseptica (Bb) vaccine, when adjuvanted with alum, does not elicit adequate robust cellular immunity or effective antibody defense against Bb attacks. Unfortunately, antibiotic treatment generally represents an ineffective strategy due to the development of resistance against a broad range of antibiotics. The present study was designed to investigate the immune response, protective capabilities and underlying mechanisms of a plant oil-based adjuvant E515 formulated with inactivated Bb antigen as a potential vaccine candidate against Bordetella bronchiseptica. Immunization studies revealed that a combination of SO, VE and GS (E515) exhibited a good synergistic adjuvant effect. The E515 adjuvanted Bb vaccine was proven to be highly efficacious and induced a mixed Th1/Th2/Th17 immune response in mice, leading to a significant increase in Bb-specific IgG, IgG1 and IgG2a antibodies, proliferative lymphocyte responses and cytokine levels (by lymphocytes and serum) and effectively induced responses by CD4+ TE, TM cells and B cells. The E515 adjuvant significantly enhanced the immune protection provided by the Bb vaccine in a mice model, as indicated by a reduced bacterial burden in the lungs. Multi-omics sequencing analysis revealed that E515 functions as an adjuvant by modulating critical pathways, including cytokine-cytokine receptor interaction, the IL-17 signaling pathway and the chemokine signaling pathway. This modulation also included interactions with beneficial species of bacteria including Alistipes, Odoribacter and Colidextribacter, as well as energy and lipid-related metabolites, thus highlighting its role as an immunomodulatory agent. Collectively, our results demonstrate the huge potential of E515-Bb vaccine candidates, thus highlighting the vegetable oil original adjuvant E515 as a promising agent for the development of new veterinary vaccines.

Escherichia coli heat-labile enterotoxin B subunit as an adjuvant of mucosal immune combined with GCRV-II VP6 triggers innate immunity and enhances adaptive immune responses following oral vaccination of grass carp (Ctenopharyngodon idella)

The grass carp reovirus (GCRV) is the most major pathogen that has threatened the grass carp (Ctenopharyngodon idella) industry of China for years. Though the oral vaccine has many advantages, the current vaccines still do not provide complete protection. Therefor the exploration of new preventive strategies is urgently needed. In this study, heat-labile enterotoxin B subunit of Escherichia coli (LTB) was combined with VP6 from GCRV type II (GCRV-II) via Lactococcus lactis expression system to form a potent oral vaccine and determines if fusion of LTB to the protective vaccine antigen can enhance protection in the fish. The expression of recombinant protein was confirmed by Western-blotting and enzyme-linked immunosorbent assay. The rare minnow was set as the model for the evaluation of the experiment administrated orally. The immune response including the antibody titer and the immune-related gene expression, and the protective efficacy which included the virus loaded and the relative protection, were thoroughly investigated after the trial. The results indicated that LTB can significantly elicit a higher neutralizing antibody responses and enhanced T-cell priming, activities and proliferation in mononuclear cells from intestine, spleen and kidney tissues when compared to the VP6 vaccine alone. Moreover, the combined adjuvant can significantly up-regulate type I interferon signaling in different immune organs, especially the mucosa associated lymphoidtissue which could not be induced by VP6 along, result in the contribution of the improvement in adaptive immune responses of the fish. In addition, challenge study showed that LTB combined VP6 could greatly improve the relative percent survival of the fish during the virus infection. These results highlight that LTB has the potential value to be a mucosal adjuvant of the fish, approaching for improving the efficacy of vaccination against GCRV-II, which does elicit both non-specific and specific immune responses.

A plant-based oligomeric CD2v extracellular domain antigen exhibits equivalent immunogenicity to the live attenuated vaccine ASFV-G-∆I177L.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a deadly, highly contagious disease in both domestic pigs and wild boar. With mortality up to 100%, the disease has been making a serious impact on the swine industry worldwide. Because no effective antiviral treatment has been observed, proactive prevention such as vaccination remains the key to controlling the outbreak. In the pursuit of expediting vaccine development, our current work has made the first report for heterologous production of the viral outer envelope glycoprotein CD2v extracellular domain (CD2v ED), a proposed promising vaccine antigen candidate in the "green" synthetic host Nicotiana benthamiana. Protein oligomerization strategies were implemented to increase the immunogenicity of the target antigen. Herein, the protein was expressed in oligomeric forms based on the C-terminally fused GCN4pII trimerization motif and GCN4pII_TP oligomerization motif. Quantitative western blot analysis showed significantly higher expression of trimeric CD2v ED_GCN4pII with a yield of about 12mg/100g of fresh weight, in comparison to oligomeric CD2v ED_GCN4pII_TP, revealing the former is the better choice for further studies. The results of purification and size determination by size exclusion chromatography (SEC) illustrated that CD2v ED_GCN4pII was successfully produced in stable oligomeric forms throughout the extraction, purification, and analysis process. Most importantly, purified CD2v ED_GCN4pII was demonstrated to induce both humoral and cellular immunity responses in mice to extents equivalent to those of the live attenuated vaccine ASFV-G-∆I177L, suggesting it as the potential subunit vaccine candidate for preventing ASFV.

Trivalent outer membrane vesicles-based combination vaccine candidate induces protective immunity against Campylobacter and invasive non-typhoidal Salmonella in adult mice.

Campylobacter and invasive non-typhoidal Salmonella (iNTS) are among the most common causative agents of gastroenteritis worldwide. As of now, no single combination licensed vaccine is available for public health use against both iNTS and Campylobacter species. Outer-membrane vesicles (OMVs) are nanoscale proteoliposomes released from the surface of gram-negative bacteria during log phase and harbor a variety of immunogenic proteins. Based on epidemiology of infections, we formulated a novel trivalent outer membrane vesicles (TOMVs)-based vaccine candidate against Campylobacter jejuni (CJ), Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE). Isolated OMVs from CJ, ST and SE were combined in equal ratios for formulation of TOMVs and 5µg of the developed vaccine candidate was used for intraperitoneal immunization of adult BALB/c mice. Immunization with TOMVs significantly activated both the humoral and cellular arm of adaptive immune response. Robust bactericidal effect was elicited by TOMVs immunized adult mice sera. TOMVs immunization induced long-term protective efficacy against CJ, ST and SE infections in mice. The study illustrates the ability of TOMVs-based combination immunogen in eliciting broad-spectrum protective immunity against prevalent Campylobacter and iNTS pathogens. According to the findings, TOMVs can work as a potent combination-based acellular vaccine candidate for amelioration of Campylobacter and iNTS-mediated gastroenteritis.

Secreted protein NFA47630 from Nocardia farcinica IFM10152 induces immunoprotective effects in mice

PurposeNocardia is emerging as a common and easily neglected cause of both healthcare- and occupation-associated infections worldwide, however, human vaccines for Nocardia prevention are not yet available. In this study, we aimed to evaluate the immunoprotective effect of the NFA47630 protein, a secreted protein abundant in the N. farcinica IFM10152 supernatant.MethodsConservation and characteristics of nfa47630 were analyzed by PCR and bioinformatics. Then recombinant NFA47630 protein was cloned, expressed and purified for further antigenicity analysis. Subsequently, the ability to activate innate immunity was evaluated by examining the phosphorylation status of the MAPK signaling pathway and cytokine levels. Finally, the protective effect was evaluated on rNFA47630-immunized mice.Resultsnfa47630 was conserved in N. farcinica strains with good antigenicity. The rNFA47630 protein was expressed under the optimal conditions of 0.2 mM IPTG, 28 °C, and it can be recognized by anti-N. farcinica and anti-N. cyriacigeorgica sera, but not anti-N. asteroids, anti-N. brasiliensis, anti-N. nova and anti-Mycobacterium bovis sera. It can upregulate the phosphorylation status of ERK, JNK, P38 and the cytokine levels of TNF-α, IL-10, IL-12, and IFN-γ. In addition, mice immunized with rNFA47630 protein exhibited higher antibody titers, greater bacterial clearance ability, milder organ infection, and higher survival rates than PBS-immunized mice.ConclusionsOur data demonstrate that NFA47630 is a potential vaccine candidate for defending against N. farcinica infection.

Computational insights in design of Crimean-Congo hemorrhagic fever virus conserved immunogenic nucleoprotein peptides containing multiple epitopes.

Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to Nairoviridae family and has tripartite RNA genome. It is endemic in various countries of Asia, Africa, and Europe and is primarily transmitted by Hyalomma ticks but nosocomial transmission also been reported. Vaccines for CCHF are in early phase of clinical trial; therefore, this work is centered on identification of potential immunogenic peptide as vaccine candidates with application of different immunoinformatics approaches. Eleven conserved (>90%) peptides of CCHFV nucleoprotein were selected for CD8+ T-cell (NetMHCpan 4.1b and NetCTLpan 1.1 server) and CD4+ T-cell (NetMHCIIpan-4.0 server and Tepitool) epitope prediction. Three peptides containing multiple CD8+ and CD4+ T-cell and B-cell epitopes were identified on basis of consensus prediction approach. Peptides displayed good antigenicity score of 0.45-0.68 and predicted to bind with diverse human leukocyte antigen (HLA) alleles. Molecular docking was performed with epitopes to HLA and HLA-epitopes complex to T-cell receptor (TCR). In most of the cases, docked complex of HLA-epitope and HLA-epitopes-TCR have the binding energy close to respective natural bound peptide complex with HLA and TCR. Molecular dynamic simulation also revealed that HLA-peptide complexes have minimum fluctuation and deviation than HLA-peptide-TCR docked over 50ns simulation run. Considering these findings, identified peptides can serve as potential vaccine candidates for CCHFV disease.

Unlocking Hope: Paving the Way for a Cutting-Edge Multi-Epitope Dengue Virus Vaccine.

Dengue fever is a significant health issue in Pakistan, demanding a vaccine effective against all the viral strains. This study employs reverse vaccinology to develop potential dengue vaccine candidates (DVAX I-III). The study thoroughly examinedconserved areas of dengue virus serotypes 1-4's structural and non-structural proteins. Key viral proteins were analyzed to find antigenic peptides, which were incorporated into vaccine candidates and potentiated with adjuvants. Computational methods predicted peptide structures and evaluated their binding to immune receptors TLR 2, TLR 4, HLA *A1101, and DRB*401. A molecular dynamics simulation lasting 100ns of the DVAX II-TLR4 complex at different time intervals clearly indicated that the ligand is attached to the receptor. Normal mode analysis assessed the stability and flexibility of these interactions. Encouragingly, all three vaccine candidates demonstrated favorable interactions with these immune receptors and the potential to induce a robust immune response. These findings suggest their safety and warrant further in vivo studies to evaluate their efficacy for clinical development.

PAMAM-Based Polymeric Immunogenic Cell Death Inducer To Potentiate Cancer Immunotherapy.

Immunogenic cell death (ICD) has been widely employed to potentiate cancer immunotherapy due to its capability to activate the anticancer immune response. Although various ICD inducers have been described, the development of synthetic materials with intrinsic ICD-inducing competency has rarely been reported. Herein, we identify a derivative of the fourth generation polyamidoamine (PAMAM) modified with multiple seven-membered heterocyclic rings, G4P-C7A, as a robust ICD inducer. G4P-C7A evokes characteristic release of damage-associated molecular patterns in tumor cells and induces efficient dendritic cell maturation. Mechanistic studies suggest that G4P-C7A can selectively accumulate in the endoplasmic reticulum and mitochondria to generate reactive oxygen species. G4P-C7A-treated tumor cells can work as potent vaccines to protect against secondary tumor implantation. Either local or systemic injection of G4P-C7A alone can effectively inhibit tumor growth by eliciting robust antitumor immune response. The combination of G4P-C7A with immunotherapeutic antibodies such as anti-PD1 (aPD-1) and anti-CD47 (aCD47) further potentiates the antitumor effect in either CT26 or 4T1 tumor model. This study offers a simple but effective strategy to induce ICD to boost cancer immunotherapy.

Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin

Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins—cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes.

The self-assembled nanoparticle-based multi-epitope influenza mRNA vaccine elicits protective immunity against H1N1 and B influenza viruses in mice.

The influenza virus is recognized as the primary cause of human respiratory diseases, with the current influenza vaccine primarily offering strain-specific immunity and limited protection against drifting strains. Considering this, the development of a broad-spectrum influenza vaccine capable of inducing effective immunity is considered the future direction in combating influenza. The present study proposes a novel mRNA-based multi-epitope influenza vaccine, which combines three conserved antigens derived from the influenza A virus. The antigens consist of M2 ion channel's extracellular domain (M2e), the conserved epitope of located in HA2 of hemagglutinin (H1, H3, B), and HA1 of hemagglutinin. At the same time, trimeric sequences and ferritin were conjugated separately to investigate the immune effects of antigen multivalent presentation. Immunization studies conducted on C57BL/6 mice with these vaccines revealed that they can elicit both humoral immunity and CD4+ and CD8+ T cell responses, which collectively contribute to enhancing cross-protective effects. The virus challenge results showed that vaccinated groups had significantly reduced lung damage, lower viral loads in the lungs, nasal turbinates, and trachea, as well as decreased levels of pro-inflammatory cytokines. These findings clearly demonstrate the wide range of protective effects provided by these vaccines against H1N1 and B influenza viruses. The present finding highlights the potential of mRNA-based influenza vaccines encoding conserved proteins as a promising strategy for eliciting broad-spectrum protective humoral and cellular immunity against H1N1 and B influenza viruses.

Outer membrane vesicles (OMVs) from Tenacibaculum maritimum as a potential vaccine against fish tenacibaculosis

Outer membrane vesicles (OMVs) have been gained increasing attention in vaccinology due to their ability to induce strong protective humoral and cell-mediated immunity. The Gram-negative bacterium Tenacibaculum maritimum, the causative agent of marine tenacibaculosis, poses a significant challenge to the global aquaculture industry due to its difficult prophylaxis. In previous studies, we demonstrated that OMV production is a key virulence mechanism in T. maritimum. Building on this, the present study aimed to evaluate the efficacy of a natural, encapsulated multi-antigen vaccine made from adjuvant-free, crude T. maritimum OMVs (Tm-OMVs). A vaccination experiment using SP9.1-OMVs was conducted in juvenile turbot (Scophthalmus maximus L.), followed by a T. maritimum bath challenge. Immune responses in the turbot were assessed by measuring anti-Tm antibody levels and analyzing the expression of eight key immune-related genes (il-1β, il-8, il-22, pcna, c3, cd4-1, ifng2, cd8α). The results showed that immunization with SP9.1-OMVs provided significant protection against T. maritimum infection (RPS = 70 %). Vaccinated fish exhibited a dose-dependent increase in anti-Tm antibody titers in blood plasma, along with rapid induction of both innate (il-1β, il-8, il-22, c3) and adaptive (cd4-1, ifng2, cd8α) immune genes as early as 4 h post-bath challenge. These findings offer new insights into the early immune response of turbot following T. maritimum infection and could serve as a foundation for developing novel OMV-based vaccines.

TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice

ABSTRACT Epstein–Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

MRNA vaccines for infectious diseases - advances, challenges and opportunities.

The concept of mRNA-based vaccines emerged more than three decades ago. Groundbreaking discoveries and technological advancements over the past 20 years have resolved the major roadblocks that initially delayed application of this new vaccine modality. The rapid development of nucleoside-modified COVID-19 mRNA vaccines demonstrated that this immunization platform is easy to develop, has an acceptable safety profile and can be produced at a large scale. The flexibility and ease of antigen design have enabled mRNA vaccines to enter development for a wide range of viruses as well as for various bacteria and parasites. However, gaps in our knowledge limit the development of next-generation mRNA vaccines with increased potency and safety. A deeper understanding of the mechanisms of action of mRNA vaccines, application of novel technologies enabling rational antigen design, andinnovative vaccine delivery strategies and vaccination regimens will likely yield potent novel vaccines against a wide range of pathogens.