current vaccine Research Articles (Page 1)

The current dengue vaccine landscape, with a focus on TAK-003 (Qdenga®).

The production of antibodies against viral structural proteins such as the spike (S) and the nucleocapsid (N) is a hallmark of SARS-CoV-2 infection. The N protein contains several immunogenic regions. In this work we analysed epitope specificity and avidity of anti-N antibodies in COVID-19 patients. Eighty-nine COVID-19 patients were recruited. IgG, IgA, IgM antibodies to recombinant N protein and to 6 different peptides containing predicted B epitopes were measured by ELISA. Antibody avidity was evaluated by chaotropic ELISA. Anti-N IgG, IgA, and IgM were detected in 59%, 41% and 30% respectively; in 11% cases anti-N IgG are the only antibodies present in COVID patients. IgG and IgA anti-N antibodies levels correlate with levels of IL-6 and inversely with PaO2/FiO2 ratio (p < 0,005). Anti-N IgG displayed medium avidity in 51% and high avidity in 49% COVID patients; anti-N avidity was negatively correlated with PaO2/FiO2 (p < 0,05). Median anti-N antibody levels were similar in discharged or deceased patients and antibody avidity was not correlated with outcome. Among peptides, N366-388 is the most frequently recognized by IgG, IgA and IgM antibodies followed by N380-400, bound by patients IgG and IgA but anti-N380-400 IgG display higher avidity than anti-N366-388 IgG. These results indicate that anti-N antibodies are characterized by medium-high avidity and preferentially bind the COOH-terminus of the nucleoprotein. Anti-N antibodies, especially directed towards specific epitopes, might be relevant for the course of the infection, and their induction might improve current vaccination strategies.

A multicomponent Fc-fused subunit vaccine induces cross-protective immunity against porcine reproductive and respiratory syndrome virus QYYZ-like and NADC30-like strains.

Background/Objectives: Meningococcal disease is primarily caused by serogroups A, B, C, W, and Y. Current US vaccination recommendations include routine serogroup A/C/W/Y (MenACWY) vaccination (ages 11-12 and 16 years) and a two-dose, 0-, 6-month MenB vaccination series (age 16-23 years) based on shared clinical decision-making. Administration of the first-in-class Pfizer pentavalent MenABCWY vaccine (PenbrayaTM), which received US licensure in 2023 as a two-dose, 0-, 6-month series, is endorsed when the MenACWY and MenB vaccines are recommended at the same visit. This study evaluated the immunogenicity and safety of two extended two-dose schedules of MenABCWY in healthy adolescents. Methods: In this observer-blinded, phase 2b study (ClinicalTrials.gov, NCT04440176; 19 June 2020), 309 healthy 11- to 14-year-olds were randomized 1:1 to receive a 0-, 36-month or 0-, 12-month Pfizer MenABCWY schedule, which more closely aligns with current US MenACWY vaccination recommendations. Endpoints included serum bactericidal assay using human complement seroprotection rates (titers ≥ 1:8 or ≥1:16, depending on strain), seroresponse rates (≥4-fold increase from baseline titer), and geometric mean titers (GMTs). Safety was also assessed. Results: One month after the second Pfizer MenABCWY dose, serogroup A/B/C/W/Y seroprotection rates were 100% for the 0-, 36-month schedule and 96.6-100% for the 0-, 12-month schedule; seroresponse rates were 100% and 92.9-100%, respectively. GMTs generally trended higher with the 0-, 36-month schedule. Seroprotection rates through 24 months after the second dose of the 0-, 12-month schedule were 44.0-75.0% for serogroup B and 88.9-100% for serogroup A/C/W/Y). No safety issues were identified. Conclusions: These data support Pfizer MenABCWY dosing flexibility and utility within the current or possible future US meningococcal vaccination framework.

Lessons from mycobacteria: development and design of Mincle-targeting adjuvants.

Background: The global spread of monkeypox virus (MPXV) highlights an urgent need for thermostable and easily administrable vaccines. Current orthopoxvirus vaccines are limited by cold-chain dependence and inconvenient injection-based delivery. Objectives: This study aimed to develop a dissolvable microneedle (DMN) vaccine against monkeypox based on a replication-deficient orthopoxvirus platform, through systematic formulation screening, stabilization mechanism exploration, and rigorous in vivo immunogenicity evaluation. Methods: A film-based approach was adopted for efficient, high-throughput formulation screening and thermostability assessment. NTV was mixed with excipients and dried into solid films. Stability was monitored via RT-qPCR after storage at 4 °C to 40 °C. The lead formulation was physically characterized, then used to fabricate MVA-BN-loaded DMN patches, which were further evaluated for in vivo immunogenicity via immunization in BALB/c mice. Results: The optimal formulation F2 (containing dextran, L-threonine, and BSA/HSA) showed a potency loss of only ~1 log10 after 2 months at 25 °C, and <1 log10 loss after 1 week at 37 °C. SEM revealed a porous virus-entrapment morphology, and FTIR indicated enhanced hydrogen bonding between the virus and the dextran matrix. The formulation was successfully manufactured into DMNs that dissolved within 5 min. In mice, these DMNs elicited robust MPXV-specific IgG and neutralizing antibody responses, with immunogenicity comparable to that induced by conventional intramuscular injection. Conclusions: This study successfully established a thermostable formulation and dissolvable microneedle delivery platform for replication-deficient orthopoxvirus vaccines against monkeypox. The optimized DMN vaccine induced robust MPXV-specific immune responses in mice with immunogenicity comparable to intramuscular injection, addressing the core limitations of current vaccines and providing a promising solution for monkeypox prevention.

Conventional type 1 dendritic cells (cDC1s) are specialized for cross-presenting tumor antigens and determining the efficacy of immunotherapies, including immune checkpoint blockade and adoptive cell therapy. However, their rarity and tumor-induced dysfunction severely limit CD8 T cell priming and represent a central bottleneck to therapeutic efficacy. While strategies such as anti-DEC-205-mediated antigen delivery and Flt3L-driven DC expansion can enhance host DC function, their reliance on functional cDC1s remains a significant constraint. We developed Tim-3-targeted vaccines by conjugating tumor antigens or neoantigens to anti-Tim-3 antibodies. These vaccines delivered antigens to both cDC1s and cDC2s, and elicited robust, durable CD8 T cell responses. Remarkably, Tim-3-targeted vaccines endowed cDC2s with efficient cross-presentation capacity that matched that of cDC1s. In tumor-bearing mice or in CD11c-β-cateninactive mice, which model β-catenin-driven DC dysfunction, Tim-3-targeted vaccination restored cross-priming and counteracted tumor- and DC-mediated immunosuppression. In Batf3-/- mice lacking cDC1s, anti-Tim-3-based vaccines still elicited significant CD8 T cell cross-priming and tumor control-albeit both were reduced compared to wild-type mice- demonstrating that cDC1s contribute to but are not essential for Tim-3-targeted vaccine-induced CD8 T cell priming and anti-tumor efficacy. Strikingly, a single dose of anti-Tim-3-neoantigen vaccination eradicated large established MC38 tumors in a CD8 T cell-dependent manner. Together, these data identify Tim-3-targeted vaccines as a next-generation cancer vaccine platform that broadens DC engagement, reduces reliance on cDC1s, and overcomes tumor- and DC-mediated immunosuppression, addressing key limitations of current DC-based cancer vaccines.

Porcine transmissible gastroenteritis virus (TGEV) remains a critical economic threat to the global swine industry due to its near 100% mortality rate in newborn piglets within 5 days of age; however, current vaccine strategies, such as attenuated vaccines, are often limited by biosafety concerns, whereas traditional inactivated vaccines, while resolving biosafety issues, exhibit poor immunogenicity. To address these limitations, this study aimed to develop a novel subunit vaccine by engineering self-assembling ferritin nanoparticles engineered to display the TGEV Spike protein receptor-binding domain (S-RBD). By fusing the S-RBD to the N-terminus of ferritin via a flexible linker, we generated eukaryotic expression plasmids and produced the recombinant proteins at scale using a lentiviral-transduced ExpiCHO cell system. Subsequent characterization via SDS-PAGE, Western blotting, and transmission electron microscopy (TEM) revealed that both TGEV-S-RBD-FR and ferritin scaffolds were successfully expressed at their predicted molecular weights of 72 kDa and 40 kDa, respectively. Critically, TEM and particle size analysis confirmed that these constructs assembled into monodisperse, spherical nanoparticles, with a diameter increase from 15 nm to 25 nm, validating the successful external display of the S-RBD. Collectively, these results demonstrate the successful development of a nanoparticle platform, offering a promising and highly programmable strategy for the prevention and control of TGEV.

Influenza B virus (IBV) undergoes continuous genetic mutations that can affect vaccine effectiveness and immune evasion. Although considerable research on IBV epidemiology exists globally, understanding of its genetic behavior in Saudi Arabia remains limited. This study characterized the molecular epidemiology of IBV in Riyadh, Saudi Arabia, during the 2024-2025 influenza season and evaluated compatibility with the current vaccine strain. Nasopharyngeal samples (n = 363) were collected from individuals presenting with influenza-like illness at King Khalid University Hospital in Riyadh. Detection and subtyping of IBV were performed using RT-PCR. Complete sequencing of the hemagglutinin (HA) and neuraminidase (NA) genes was conducted on confirmed IBV isolates (n = 7), followed by phylogenetic analysis, amino acid substitution mapping, and glycosylation site prediction. Of the 363 samples analyzed, 68 (18.7%) tested positive for IBV, with the majority occurring in adult females aged 15-64 years. Phylogenetic analysis revealed that all seven IBV isolates belonged to the Victoria lineage under subclade V1A.3a.2, corresponding to the current vaccine strain and strains from the 2022-2023 epidemic season. However, molecular analysis identified two substitutions (D129N and D197E) located in antigenic loop-150 and 190-helix, respectively, in the HA polypeptide that distinguished our strains from vaccine strain B/Austria/1359417/2021. Importantly, the N-glycosylation site at position 169 (NKT), which was present in B/Riyadh/1/2010, has been lost in the IBV strains circulating during 2020-2025. While phylogenetic clade compatibility indicates potential vaccine efficacy, the identified amino acid variations and loss of the glycosylation site underscore the necessity for ongoing molecular surveillance to monitor antigenic changes and evaluate vaccine effectiveness within the Saudi Arabian population.

Background: In South Korea, foot-and-mouth disease (FMD), a highly contagious viral infection that affects cloven-hoofed animals, has led to the implementation of a bivalent FMD vaccination program. The current FMD vaccination strategy involves intramuscular (IM) administration to the shoulder region of the swine. However, this method is associated with adverse reactions at injection sites. Our previous studies have demonstrated that intradermal (ID) vaccination eliminates these side effects while maintaining immunogenicity comparable to that of IM vaccination. This study aimed to assess the early immune response induced by ID vaccination and compare its protective ability against FMDV serotype O with that of a commercial IM vaccine recently used in South Korea. Methods: An ID FMD vaccine was evaluated using two adjuvants, ISA 207 (50%) and EMULSIGEN-D (15%). Virus neutralization (VN) titers and structural protein levels were measured to compare efficacy across groups. To assess the early protective efficacy of ID vaccination, viral challenge experiments were conducted at 7 and 14 days post-vaccination (dpv). Results: Swine vaccinated via the ID route exhibited no clinical symptoms at 14 dpv, indicating effective early protection against FMD (O/AS/SKR/2019). In addition, no side effects of FMD ID vaccination were observed. Conclusions: These results suggest that ID vaccination could serve as a viable alternative to conventional IM vaccination, which is frequently associated with adverse effects. Importantly, this study demonstrates that ID vaccination can provide effective early protection within 7-14 days post-vaccination, highlighting its potential utility for emergency outbreak control.

Current SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccines have shown robust induction of neutralizing antibodies and CD4+ T cell activation; however, CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurpose our DNA origami vaccine nanotechnology DoriVac to target infectious viruses, namely, SARS-CoV-2, HIV and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific heptad repeat 2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induces neutralizing antibodies, Th1 CD4+ T cells and CD8+ T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validate that DoriVac, when conjugated with antigenic peptides or proteins, induces promising cellular and humoral immune responses in human cells. Moreover, DoriVac bearing full-length SARS-CoV-2 spike protein achieves immune responses comparable to current mRNA vaccine platforms while potentially reducing storage constraints. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities, underscoring its potential future use.

Pandemic influenza remains a persistent global threat with the potential to cause widespread morbidity, mortality, and economic disruption. Despite decades of preparedness efforts, current influenza vaccine systems remain constrained by long production timelines, early strain-selection requirements, and limited flexibility once a pandemic is underway. The COVID-19 pandemic fundamentally reshaped expectations for vaccine development and deployment, demonstrating that platform-based technologies, particularly messenger RNA (mRNA) vaccines, can deliver safe and effective vaccines at unprecedented speed when supported by regulatory readiness, manufacturing capacity, and coordinated public-private investment. Drawing on lessons from COVID-19, recent Phase III clinical trial data for seasonal influenza mRNA vaccines, and global preparedness initiatives such as the 100 Days Mission, this expert perspective examines how mRNA and other next-generation vaccine technologies could strengthen preparedness for a future influenza pandemic. It reviews evidence related to platform speed, clinical performance, manufacturing adaptability, regulatory pathways, and global access, while also highlighting emerging scientific frontiers, including artificial intelligence-augmented immunogen design and innovations in vaccine delivery. It argues that sustained investment in adaptable vaccine platforms, coupled with advances in delivery, manufacturing, and data-driven design, will be critical to improving global readiness and reducing the impact of the next influenza pandemic.

Current vaccine research still confronts multiple challenges, and epitope-focused vaccine design serves as an effective technical approach to address these issues. Antigens harbor multiple epitopes; however, the number of epitopes capable of triggering significant antibody responses in vaccinated individuals remains undefined. This study aimed to determine the number of non-overlapping epitopes-designated "effective epitopes" hereafter-that trigger significant antibody production in vaccinated individuals when presented in distinct PlpE epitope-chimeric proteins. Herein, chimeric proteins incorporating varying numbers of PlpE non-overlapping B-cell epitopes were generated. By analyzing serum antibody responses in vaccinated individuals, we defined the quantitative characteristic of PlpE-derived effective epitopes. The total number of PlpE effective epitopes in vaccinated individuals was 2.6 (95% CI: 1.909-3.201) for full-length PlpE and 1.2 (95% CI: 0.5426-1.857), 0.9 (95% CI: 0-1.820), and 0.2 (95% CI: 0-0.5016) for the PlpE chimeric proteins (PlpE-VP60P, PlpE-BcfA, PlpE-PtfA), respectively. With an increase in the number of PlpE non-overlapping epitopes incorporated into the chimeric proteins, the number of PlpE effective epitopes exhibited a trend of initial increase followed by a decrease. Ultimately, the average total number of effective epitopes across all PlpE chimeric proteins did not exceed 3, with the highest number 2.1 (95%CI: 1.572-2.628). In conclusion, the number of PlpE non-overlapping epitopes on an antigen, that trigger significant antibody responses in each vaccinated individual, is very limited.IMPORTANCEEpitopes underpin the antigenicity of protein antigens. Although the concept of antigenic epitopes has been proposed over 50 years, our understanding on epitopes remains incomplete. Multiple antigenic epitopes can be identified on a single antigen, while the number of these epitopes that function in vaccinated individuals remains unclear-a gap hindering the rational design of vaccines. In previous studies, we identified six non-overlapping epitopes of Pasteurella multocida PlpE. Herein, we found that the total number of non-overlapping epitopes-capable of significantly triggering antibody production-that are present in PlpE chimeric proteins does not exceed three per vaccinated individual. This finding offers important insights for rational vaccine design: given the highly limited number of non-overlapping epitopes that function in vaccinated individuals, only a limited number of epitopes can be grafted onto scaffold proteins. Epitope-focused vaccine design must, therefore, account for competitive interactions between epitopes on the new antigen.

A self-assembling ferritin nanoparticle-based trivalent vaccine of gB/gE/gH elicits potent immune responses against varicella-zoster virus.

Cyclical epidemics of pertussis, also known as whooping cough, continue to occur despite vaccination, because current vaccines fail to suppress colonisation by, and transmission of, the causative agent Bordetella pertussis. We aimed to show the safety of B pertussis controlled human infection delivered in an outpatient setting, as well as identify immunological correlates of protection against B pertussis colonisation, to guide the future development of pertussis vaccines. This open-label, phase 1, controlled human infection study was conducted at University Hospital Southampton, Southampton, UK. Healthy volunteers aged 18-55 years who had received a whole-cell pertussis vaccine in childhood were inoculated intranasally with 105 colony-forming units of wild-type B pertussis strain B1917. Volunteers were monitored as outpatients for 28 days to assess safety, colonisation, and B pertussis-specific immunological parameters. Individuals who shared a bedroom with inoculated volunteers were enrolled to measure transmission to close contacts. After approximately 90 days, volunteers who agreed to participate in a rechallenge phase of the study were re-inoculated with the same dose of B pertussis. Volunteers received azithromycin 14 days after each inoculation. The primary objective was to assess the safety of delivering this controlled human infection model on an outpatient basis; safety endpoints were the occurrence of possible or confirmed pertussis and unsolicited or serious adverse events. Secondary objectives were the assessment of immunological biomarkers of protection from colonisation and the assessment of transmission from volunteers to close contacts. All volunteers who received the inoculum were included in the safety analysis, and all participants who completed follow-up to day 14 were included in the per-protocol population for colonisation and immunological analysis. This trial is registered at ClinicalTrials.gov, NCT03751514, and is ongoing. Between Aug 29, 2019 and March 6, 2023, 77 volunteers were screened and 51 were enrolled and inoculated, of whom 50 completed follow-up to day 14 post-inoculation. 20 (40%) of these 50 volunteers became colonised with B pertussis. One volunteer developed symptoms suggestive of possible pertussis after initial inoculation; this volunteer tested negative for B pertussis throughout the study and all symptoms resolved within 4 days. Adverse events were mostly mild to moderate, with no significant increase in the reporting of any individual symptom by colonised volunteers. All unsolicited adverse events were assessed as either unlikely to be related or unrelated to B pertussis infection, with no increase in the frequency of these events seen in colonised volunteers. There were no serious adverse events and no treatment-related deaths. Compared with those who became colonised with B pertussis, non-colonised volunteers had significantly higher pre-inoculation serum IgG antibody concentrations against several acellular pertussis vaccine antigens (pertussis toxin [p=0·028], pertactin [p=0·037], and filamentous haemagglutinin [p=0·024]); higher nasal (p=0·022) and serum (p=0·044) IgA antibody concentrations against whole B pertussis; higher serum IgA antibody concentrations specific to filamentous haemagglutinin (p=0·024); and higher peripheral T-helper (Th)-22-cell responses to pertussis toxin (p=0·0045) and filamentous haemagglutinin (p=0·029). After inoculation, only colonised volunteers showed seroconversion, IgA and IgG binding to B pertussis, and increases in B pertussis-specific IgG-secreting memory B-cell frequencies by day 28. Th17 responses to pertussis toxin were increased (p=0·039) and Th22 responses to filamentous haemagglutinin were decreased (p=0·014) in non-colonised volunteers. Of the 13 volunteers who became colonised after initial inoculation and were re-inoculated, only one (8%) became colonised after re-inoculation. Transmission from volunteers to 14 enrolled individuals with whom they shared a bedroom was not detected. Our findings suggest that controlled human infection with B pertussis in an outpatient setting is safe. Higher humoral and CD4+ T-cell responses with specificity to acellular pertussis vaccine antigens are associated with protection against colonisation by B pertussis after experimental challenge. This technique could enable the testing of potential novel vaccines or formulations for sustained protection against infection and transmission. EU Horizon 2020 (Innovative Medicines Initiative) and the National Institute for Health and Care Research Southampton Biomedical Research Centre.

The Langya virus (LayV), an emerging zoonotic henipavirus with pandemic potential and high fatality risks akin to Nipah and Hendra viruses. It underscores an urgent public health need for preventive solutions, given its lack of approved vaccines or therapies. Current RNA virus vaccine strategies, reliant on traditional live/inactivated approaches, face safety and scalability limitations, while multi-epitope designs for LayV’s structural proteins (N, P, M, F, G, and L) remain unexplored. This study aimed to computationally design a safe, specific, and scalable multi-epitope vaccine targeting LayV’s glycoproteins and fusion protein. We Used immunoinformatics tools (VaxiJen, NetCTL, IEDB) five antigenic proteins were prioritized, and 12 CTL, 7 HTL, and 4 B-cell epitopes were selected after screening. Three constructs (VCa, VCb, VCc) were engineered with adjuvants (L7/L12) and linkers (GPGPG/AAY), followed by a stability check using molecular docking and dynamics simulations (GROMACS). The constructs VCb emerged as the lead candidate, which was further suggested for experimental validation, exhibiting superior solubility (0.846), structural stability (instability index: 28.8), strong TLR4 binding (-336.5 kcal/mol), elevated β-strand content (20.8 %), and robust simulated immunity (IgG1: ∼24,000; IFN-γ: ∼5,000 ng/ml). Codon optimization (CAI >0.95, GC 52–55 %) confirmed the feasibility of an efficient E. coli expression system. This computational framework offers a quick and reliable approach for designing a LayV vaccine and highlights VCb as a promising multi-epitope vaccine candidate that deserves further experimental validation.

The endemic dilemma: why whole sporozoite malaria vaccine efficacy falls in the field.

Influenza A and Mycoplasma pneumoniae (M. pneumoniae) are common respiratory pathogens, causing severe co-infections in clinical diseases. Current vaccines have failed to provide comprehensive protection against both of the pathogens, highlighting the requirement of integrated solution. In this study, a novel dual-target multi-epitope vaccine was developed based on the immunoinformatics method. Based on the consistent sequences, we used the HA and NA proteins of influenza A virus, and the p1, p65, HMW1-3 proteins of M. pneumoniae to determine the immunodominant T- and B-cell epitopes. The designed vaccine included 21 linear B-cell epitopes, 34 CTL epitopes and 19 HTL epitopes from influenza A virus and M. pneumoniae. The selection was based on antigenicity, immunogenicity, and alignment with previously validated epitopes. Structural and physicochemical assessments indicated that the vaccine had high stability, solubility, and minimal allergy risk. Molecular docking with TLR3 and TLR4 receptors revealed strong binding, suggesting robust immune activation. Population coverage analysis showed the vaccine could cover 97.07% of the global population, with high efficacy across key regions such as North America and East Asia. In this study, we provided an immunoinformatics approach for vaccine design.

Short-lived, clade-specific immune responses with limited mucosal priming are limitations of current COVID-19 mRNA vaccines. We have developed a nasal booster vaccine candidate that induced robust, sustained, cross-clade, systemic, and mucosal protective immunity. Two recombinant Clec9A-specific monoclonal antibodies fused to the receptor binding domain (RBD) from Omicron XBB.1.5 and SARS-CoV-1 were generated. In Comirnaty mRNA–vaccinated mice, boosting with both constructs combined (Clec9AOMNI) induced cross-clade neutralizing antibodies and T cell responses that were greater in magnitude and more sustained compared with bivalent Comirnaty (BC) mRNA vaccine booster. Persistence of RBD-specific follicular helper CD4+ T cells, germinal center B cells, and long-lived plasma cells that facilitated affinity maturation correlated with detection of triple cross-reactive B cells binding the RBDs of ancestral SARS-CoV-2, XBB.1.5, and SARS-CoV-1. Remarkably, intranasal boosting with Clec9AOMNI elicited robust and durable immunity across the upper and lower airways while concurrently boosting the systemic immunity to levels matching or exceeding those from systemic boosting. Correspondingly, Clec9AOMNI nasal booster conferred superior protection against SARS-CoV-2 challenge compared with BC mRNA booster, with undetectable viral titers in the respiratory tract. Hence, Clec9AOMNI is a promising nasal booster vaccine candidate that has the potential to mitigate pandemic threats from emerging sarbecoviruses.

Background: Non-typhoidal Salmonella (NTS) is a major foodborne pathogen, with poultry products, especially eggs, being the primary source of human infections. Current serovar-specific poultry vaccines effectively reduce targeted Salmonella serovars but may inadvertently promote the emergence of untargeted serovars within poultry flocks. Therefore, novel vaccine candidates providing broad cross-serovar protection are needed to improve overall effectiveness of Salmonella control programs. Objectives: This study evaluated the immunogenicity of the novel subunit vaccine candidate InvG and assessed its ability to reduce Salmonella colonization in vaccinated laying hens and their progeny through maternally derived antibodies transferred via egg yolk. Methodology: Three experiments were performed. Experiment I evaluated the immunogenicity of purified recombinant InvG by (a) measuring anti-InvG antibodies using an enzyme-linked immunosorbent assay (ELISA) and (b) completing transcriptomic profiling of immune responses in vaccinated chickens. Vaccinated chickens were subsequently challenged with Salmonella Enteritidis to assess the efficacy of anti InvG antibodies in reducing intestinal colonization of Salmonella. Experiment II involved immunizing hens with InvG, to evaluate passive transfer of antibodies via egg yolk and the protective efficacy of maternally derived antibodies against Salmonella challenge. Passive transfer was assessed by measuring IgY antibodies in hen serum, egg yolk, and progeny serum, as well as secretory IgA (sIgA) antibodies in progeny intestinal washings using ELISA. Protective efficacy was evaluated by orally challenging one-day-old chicks with three different Salmonella serovars. Experiment III assessed the persistence of anti-InvG antibodies in the serum of vaccinated hens and their transfer into eggs following two doses of InvG. Results: InvG vaccination induced robust IgY antibody responses in hens, with efficient maternal antibody transfer to progeny via egg yolk. A statistically significant reduction in Salmonella colonization was observed in both vaccinated hens and their progeny. Conclusions: These findings demonstrate that InvG represents a promising subunit vaccine candidate for Salmonella control in poultry and warrants further investigation towards development as a broadly protective commercial poultry vaccine against Salmonella.