Search Results (1,054)

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a fatal and highly contagious disease, resulting in enormous losses to the global swine industry. No licensed vaccines or effective therapeutics are currently available to control ASFV infection. Interferons (IFNs) serve as key mediators of host antiviral immunity by inducing interferon-stimulated genes (ISGs), but the specific mechanisms by which individual ISGs restrict ASFV replication remain unclear. Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3, also called ISG60) has been shown to exhibit antiviral activity against various viruses, but its role in ASFV infection has not been previously studied. Here, we used porcine alveolar macrophages (PAMs), the primary target cells of ASFV, to investigate IFIT3’s function in ASFV replication. We found that overexpression of IFIT3 inhibited ASFV replication, while its knockdown enhanced viral propagation. Mechanistically, IFIT3 directly blocked ASFV adsorption to host cells, thereby suppressing all subsequent stages of the viral cycle. IFIT3 also specifically interacted with ASFV F334L, an early viral gene product that encodes the small subunit of ribonucleotide reductase, a key enzyme for viral DNA synthesis. Additionally, IFIT3 positively regulated the STAT1/TBK1/IRF3 signaling axis: its overexpression increased phosphorylation of TBK1 and IRF3, as well as the protein level of STAT1, while IFIT3 knockdown attenuated activation of these molecules. Transcriptomic analysis of IFIT3-knockout PAMs revealed significant suppression of innate immune pathways, including type I interferon, JAK-STAT, and RIG-I-like receptor pathways, along with downregulated expression of core antiviral molecules such as ISG15, MX1, and STAT1. Conversely, pathways related to viral adsorption, endocytosis, and cytoskeleton were activated, and pathways involved in protein translation initiation, endoplasmic reticulum stress, and autophagy were dysregulated, creating a favorable intracellular environment for ASFV replication. In conclusion, IFIT3 restricts ASFV replication possibly by inhibiting viral adsorption and promoting innate immune signaling, identifying it as a potential therapeutic target against ASFV. This study’s limitation is its in vitro PAM model; future work will validate IFIT3’s role in vivo and develop targeted inhibitors. Full article

Human metapneumovirus (HPMV) is a significant pathogen that causes lower respiratory tract infections. Given the weak immunogenicity thereof, and the few relevant studies, the utility of the viral membrane protein G as a vaccine remains controversial. In this study, the G extracellular domain (RMG) of HMPV was expressed either alone or fused with the cholera toxin B subunit (CTB) and “cross-reacting material 197” (CRM197) carrier proteins (giving G-CTB/G and CRM197), to enhance immunogenicity. The non-glycosylated G protein (REG) expressed in Escherichia coli served as a control. SDS-PAGE and anti-His tag Western blotting verified that each protein was successfully expressed and correctly identified. BALB/c mice were immunized with each protein and subjected to challenge with HMPV. The results showed that, although immunization with RMG alone failed to induce potent neutralizing antibodies, it modestly reduced viral loads in the lungs of mice. However, the pathological damage caused by lung inflammation was more aggravated than that of the control challenge group. The level of specific IgG antibody induced by the recombinant G-CTB was significantly higher than that elicited by RMG. Compared to the RMG group, the viral load in the lungs of the G-CTB group tended to be reduced. Also, the damage caused by lung inflammation was significantly alleviated. Our study proves that HMPV G may be a valuable antigen in terms of HMPV vaccine development and offers a promising strategy for modulating the immunogenicity and safety thereof. Full article

Background/Objectives: Several subunit vaccines for tuberculosis (TB), such as MVA85A and H4:IC31, have not demonstrated ideal protective efficacy in clinical trials, which may be attributed to their limited antigenic profile and lack of effective latency-associated antigens. In this study, we combined bioinformatics with experimental validation to screen for latency-associated antigens that have immune-protective effects. Methods: Highly expressed antigens were identified from models related to latent infections, such as hypoxia and nutritional starvation. Their physicochemical properties and immunogenicity were predicted using online tools such as Expasy-ProParam, IEBD, and VaxiJen. The immunogenicity of these antigens was then evaluated in multiple mycobacterium infection models. Finally, a systematic evaluation of the immune response and protective effects induced by the candidate antigens was performed in a mouse model using intracellular cytokine detection, mycobacterium growth inhibition assays (MGIAs), antibody-dependent cellular phagocytosis (ADCP), and a latent tuberculosis infection (LTBI) mouse model. Results: The antigen Rv2656c is highly expressed in the nutritional starvation model and demonstrates strong immunogenicity in both infected humans and cattle. Moreover, Rv2656c exerted a significant inhibitory effect against Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium avium (M. avium) infections in MGIA. The humoral immune response elicited by Rv2656c enhanced the phagocytosis and killing of Mycobacteria by macrophages in vitro. Furthermore, in a mouse model of LTBI established using the attenuated M. tuberculosis H37Ra strain, treatment with Rv2656c significantly decreased the bacterial load in the lungs of the mice. Conclusions: Latency-associated Rv2656c may serve as an immune-protective antigen, offering potential for the development of novel multi-stage antigen subunit vaccine against TB. Full article

Nipah virus (NiV) is an animal-borne RNA virus of the genus Henipavirus that poses a significant global health threat. This threat is driven by the virus’s high mortality rate, its capacity to cause epidemics, and the lack of licensed therapeutic interventions or vaccines. Since its initial identification during the 1998–1999 outbreak in Malaysia and Singapore, recurrent episodes have occurred primarily in Bangladesh and India, with mortality rates frequently exceeding 70%. Fruit bats of the genus Pteropus serve as the biological host for the virus. Transmission to humans occurs via contact with infected wildlife, consumption of contaminated products, such as freshly harvested date palm sap, or direct person-to-person exposure. Other modes of transmission, such as transplacentally or via breast milk, are still under investigation. The clinical presentation of NiV infection varies widely, from mild flu-like symptoms to life-threatening respiratory disease and acute encephalitis. It frequently attacks the nervous system, which can lead to coma, permanent neurological damage, or relapsing encephalitis. The virus enters host cells via ephrin-B2/B3 receptors, enabling systemic dissemination and infiltration of the central nervous system. Diagnosis relies primarily on RT-PCR and serological assays, and virus isolation requires high-containment laboratories. Management remains largely supportive, as no approved antiviral therapy exists. Experimental agents, such as remdesivir, favipiravir, and monoclonal antibodies such as m102.4, have shown promise in preclinical studies. Multiple vaccine platforms—including subunit, viral vector, mRNA, and nanoparticle-based approaches—are under development, though none is yet licensed for human use. Strengthened surveillance, infection control measures, and continued research are essential to mitigate the threat posed by this emerging pathogen. This review summarizes current knowledge on NiV, including its virology, epidemiology, pathogenesis, transmission, and recent progress in therapeutic and vaccine development. Full article

Avibacterium paragallinarum (A. paragallinarum) is the primary causative agent of infectious coryza in chickens. Infection often leads to growth retardation in broilers and a 10% reduction in egg production, reaching over 40% in laying hens. The problem is particularly severe under intensive farming conditions, significantly jeopardizing global poultry health and farming profitability. From a ‘One Health’ perspective, this not only disrupts the stability of the food supply chain, but also increases antibiotic usage due to disease prevention and control needs, thereby aggravating antimicrobial resistance (AMR) and posing a global public health challenge. This review systematically summarizes advances in the pathogenesis of A. paragallinarum and the protective immunity induced by subunit vaccines. It focuses on the infection mechanisms of A. paragallinarum, emphasizing its colonization strategies in the infraorbital sinus and nasal epithelium of chickens, and analyzes the roles of key virulence factors such as hemagglutinin and capsule in adhesion, colonization, and immune evasion. We integrate the tissue-specific pathogenesis of A. paragallinarum with the role of respiratory commensal microbiota in facilitating infection, providing an in-depth analysis of the bacterium’s key immune evasion strategies, thus offering novel insights into host–pathogen-microbiome interactions. Concurrently, to the best of our knowledge, this review provides the first comprehensive overview of current developments in subunit vaccines and their immunoprotective properties, with special attention to limitations in eliciting mucosal immune responses. By delving into the pathogen-host interaction mechanisms, this review aims to inform the optimization of subunit vaccine design and immunization strategies. Ultimately, it seeks to establish a theoretical basis and practical framework for precise control of A. paragallinarum. Full article

Background: Pertussis toxin (Ptx) is a major virulence factor and protective antigen of Bordetella pertussis. Understanding its antigenic landscape is essential for improving vaccine design. This study aimed to compare the linear epitope profiles of Ptx recognized by antibodies from vaccinated children and mice, identifying conserved and species-specific immune targets across subunits S1–S5. Methods: Two libraries of overlapping 14-mer peptides spanning the full-length Ptx sequence were synthesized. Sera from children and mice immunized with the whole-cell pertussis vaccine were analyzed to map antibody-binding regions. Comparative and structural analyses were performed to evaluate epitope distribution and recognition patterns. Results: Murine sera recognized 12 major epitopes, whereas children’s sera identified 24. Eleven epitopes were shared between species, mainly in subunits S1 (Ep3–5, 7, 9, 10), S3 (Ep20, 21, 25, 26), and S5 (Ep32), although minor positional shifts were observed. Eight epitopes were unique to children’s sera, located in S1 (Ep1, 6, 8), S3 (Ep22–24), and S4 (Ep27, 29–30). In the S2 subunit, four distinct epitopes were identified for each species, while only one mouse-specific epitope was detected in S4 (Ep28). Structural analysis revealed non-uniform antibody recognition, with dominant targeting of S3 and conserved antigenic hotspots, as well as selective recognition of the catalytic S1 subunit. Fourteen novel epitopes were identified. Conclusions: These findings highlight both shared and species-specific Ptx epitopes, revealing differences between murine and human immune responses. The identified conserved regions and novel epitopes provide a basis for improved pertussis vaccine design. Full article

Brucellosis remains one of the most widespread zoonotic infections worldwide, causing serious veterinary, medical, and socio-economic consequences. The disease, caused by bacteria of the genus Brucella, affects a wide range of domestic and wild animals as well as humans, with global incidence potentially reaching 1.6–2.1 million new cases annually. The most effective approach to combating brucellosis is specific prevention through vaccination. Therefore, we conducted this review to summarize data from existing studies on modern strategies for brucellosis vaccination, types of vaccine platforms, their efficacy, safety, and applicability in veterinary and human medicine. We searched databases including PubMed, Scopus, and Web of Science to identify relevant scientific articles in English published from 1990 to 2025. The aim of this work is to conduct a systematic analysis of modern brucellosis vaccination strategies in livestock and humans, as well as to evaluate the prospects of new vaccine platforms. The review examines live attenuated, inactivated, subunit, vector, and DNA vaccines, as well as their immunological mechanisms of action, advantages, and limitations of application. This information allows for a better understanding of the mechanisms of protective immunity formation and challenges related to DIVA diagnostics (Differentiating Infected from Vaccinated Animals). The “One Health” concept demonstrated the interconnection between human, animal, and environmental factors, emphasizing the need for an interdisciplinary approach to brucellosis monitoring, prevention, and control. Vector vaccines based on influenza virus (Flu-BA), developed in Kazakhstan, have shown high promise, combining immunogenicity, protective efficacy, and a favorable safety profile. Promising directions remain mRNA vaccines, nanoparticles, CRISPR/Cas9 technologies, and mucosal vaccines. Full article

Background: The recombinant zoster vaccine (RZV) has been shown to reduce the risk of dementia and delay cognitive decline. However, economic evaluations in populations with mild cognitive impairment (MCI), particularly those incorporating cognitive outcomes, remain unavailable. This study evaluated the cost-effectiveness of RZV vaccination at age 50 among Chinese adults with MCI. Methods: A decision tree–Markov model was developed from a societal perspective to assess the lifetime cost-effectiveness of RZV (Shingrix, GSK) in a cohort of 1 million immunocompetent Chinese adults with MCI receiving vaccination at the age of 50. The primary outcome was the incremental cost-effectiveness ratio (ICER), while secondary outcomes included cases averted and the number needed to vaccinate (NNV) to prevent one case of herpes zoster (HZ), postherpetic neuralgia (PHN), and dementia. A willingness-to-pay (WTP) threshold equivalent to the 2024 Chinese gross domestic product (GDP) per capita (13,121 USD) was applied. Sensitivity analyses were conducted to test the robustness of the results. Results: Over a lifetime horizon, RZV vaccination was estimated to avert 54.64% of HZ cases, 97.58% of PHN cases, and 12.28% of dementia cases compared with no vaccination, resulting in an additional 2.23 million quality-adjusted life years (QALYs) gained. The ICER was 4216.99 USD/QALY, remaining well below the WTP threshold. The corresponding NNVs were 6.25 for HZ, 24.03 for PHN, and 280.82 for dementia progression. Conclusions: RZV vaccination is cost-effective for Chinese adults aged 50 years with MCI, providing substantial health gains through reductions in both HZ burden and dementia progression. Full article

Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite’s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals—prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis. Full article

The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of pertussis. After infection with B. pertussis, PT is released and binds to its human target cells, which internalize PT. The enzyme subunit of PT is then taken up into the cytosol, where it catalyzes the ADP-ribosylation of the α-subunit of inhibitory GTP-binding proteins from the Gαi type. This ultimately leads to the development of the characteristic clinical symptoms associated with pertussis. Pertussis is a vaccine-preventable but highly infectious respiratory disease, and especially younger children are prone to develop severe pertussis. Despite the vaccination, over the past few years, increasing case numbers have been reported globally. Moreover, treatment options are strongly limited to antibiotics and symptomatic treatment. Therefore, novel therapies against toxin-mediated diseases are urgently required, while AB-type toxins such as PT are promising pharmacological targets to combat these associated diseases. To identify novel pharmacological inhibitors for AB-type toxins, huge potential lies within the human proteome/peptidome. Endogenous protein or peptide inhibitors for bacterial toxins might have evolved as part of the innate immunity and are awaited to be discovered. The scientific community is committed to identify potential candidates through targeted screening or explorative hypothesis-driven approaches. This review summarizes the recent efforts in the identification and characterization of the human body’s own proteins and peptides that inhibit PT. PT-inhibiting peptides were found by unbiased screening of peptide libraries from human hemofiltrate or hypothesis-driven evaluation, and PT-neutralizing mechanisms were discovered in cell-based approaches. The identification of endogenous peptides and proteins, e.g., defensins and α₁-antitrypsin, as potent inhibitors of PT paves the way towards the development of novel therapeutic options against pertussis. Full article

Background: The emergence of SARS-CoV-2 variants necessitates the development of effective adjuvants to enhance subunit vaccine immunogenicity. Safe adjuvants are essential to enhance the immunogenicity of SARS-CoV-2 receptor-binding domain (RBD) subunit vaccines. Traditional Chinese medicine polysaccharides are attractive candidates due to their immunomodulatory properties. Methods: Female BALB/c mice (6–8 weeks) were immunized on days 0, 7, and 21 with an RBD protein (20 μg) alone or formulated with Poria cocos polysaccharide fraction PCP-I or PCP-II (200 μg), Isatis indigotica polysaccharide, or aluminum adjuvant; PBS served as a control. RBD-specific total IgG and subclasses were quantified by ELISA on day 7 after the third immunization. Neutralizing antibody titers were measured by a pseudovirus assay on days 14, 28, and 56 after the first immunization. Splenic CD19⁺ B cells were analyzed by flow cytometry, and antigen-stimulated IFN-γ and IL-4 spot-forming cells were quantified by ELISpot. Results: PCP-II significantly increased RBD-specific total IgG and IgG1 compared with RBD alone and other formulations, whereas IgG2a and IgG2b remained unchanged. Both PCP-I and PCP-II increased neutralizing titers versus RBD alone, and PCP-II showed an earlier and sustained increase in neutralizing responses through day 56. PCP-II showed a non-significant increase in splenic CD19⁺ B cell frequency. PCP-I and PCP-II markedly increased IFN-γ-secreting splenocytes without increasing IL-4, indicating enhanced antigen-specific cellular responses. Conclusion: In this comparative evaluation of traditional Chinese medicine polysaccharide candidates in a SARS-CoV-2 RBD subunit vaccine model, PCP-II showed the most prominent adjuvant activity. PCP-II enhanced antigen-specific humoral immunogenicity, improved neutralizing antibody responses, and was associated with increased IFN-γ-related cellular responses, supporting its potential as a candidate polysaccharide adjuvant for protein subunit vaccines. Full article

Background: Epimedium is a natural herb with immunomodulatory potential, but its vaccine adjuvant properties remain poorly understood. Objective: The aim of this study was to elucidate the adjuvant effects of Epimedium and the underlying molecular mechanisms. Methods: Network pharmacology was used to identify bioactive compounds and targets of Epimedium from the TCMSP database, and immunomodulation-related targets from GeneCards and OMIM. PPI networks, KEGG/GO enrichment, molecular docking, and molecular dynamics (MD) simulations were performed. In vivo, female BALB/c mice were immunized with the Staphylococcus aureus (S. aureus) vaccine subunit HI antigen, either alone or with low- or high-dose icariin (ICA). Serum antibody responses (IgG, IgG1, IgG2a, IgG2b) were measured by ELISA. Survival against lethal S. aureus USA300 challenge was monitored. Results: Network pharmacology predicted 488 targets and 13 pathways. Core targets included IL6, TP53, EGFR, CTNNB1, HIF1A, HSP90AA1, JUN, MTOR, SRC, and AKT1. KEGG/GO analysis indicated involvement of T cell receptor and NOD-like receptor signaling pathways in inflammatory responses. Molecular docking and MD simulations confirmed stable ligand-target binding. Experimental validation showed that ICA significantly enhanced HI-specific antibody responses and induced a Th2-biased humoral immune response (IgG1/IgG2a ratio > 1), which is particularly relevant for vaccines targeting extracellular pathogens such as S. aureus. ICA also improved survival after lethal bacterial challenge. Conclusions: This study identifies potential bioactive compounds, core targets, and key pathways of Epimedium as a vaccine adjuvant. Experimentally, ICA, as a representative component, enhanced HI-specific antibody responses and conferred protection against lethal S. aureus challenge. Together, these findings offer a computational–experimental basis that may guide further mechanistic investigation. Full article

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus responsible for sporadic outbreaks of severe disease with high case fatality rates in South and Southeast Asia. Human infection occurs through spillover from natural reservoirs, primarily fruit bats, or via human-to-human transmission, and is characterized by a broad clinical spectrum ranging from asymptomatic infection to acute respiratory disease and fatal encephalitis. Following entry via ephrin-B2 and ephrin-B3 receptors, NiV exhibits marked endothelial and neuronal tropism, leading to systemic vasculitis, disruption of the blood–brain barrier, and direct infection of the central nervous system. Disease progression is driven by a complex interplay between viral replication strategies and host immune responses. NiV effectively counteracts innate immunity through multiple viral proteins that inhibit interferon signaling, while simultaneously inducing dysregulated inflammatory responses that contribute to tissue damage and multi-organ failure. Neurological involvement represents the most severe manifestation, often resulting in acute or relapsing encephalitis with long-term sequelae among survivors. Despite the severity of the disease, no licensed antiviral therapies or human vaccines are currently available. Therapeutic development has focused on neutralizing monoclonal antibodies targeting viral glycoproteins and small-molecule antivirals that inhibit viral RNA synthesis, both of which show promising results in preclinical models, but remain limited by timing and translational challenges. In parallel, several vaccine platforms—including viral vectors, mRNA-based constructs, and recombinant protein subunits—have advanced to early-phase clinical trials, demonstrating encouraging immunogenicity. Beyond biomedical interventions, effective outbreak containment relies on integrated public health strategies. The “Kerala model” highlights the importance of rapid case identification, isolation, contact tracing, and community engagement within a One Health framework to mitigate transmission and reduce mortality. This review synthesizes the current knowledge on NiV pathogenesis, immune evasion, clinical manifestations, and emerging therapeutic and vaccine strategies, while highlighting critical gaps and future directions for improving the preparedness and response to this high-consequence emerging pathogen. Full article

Background/Objectives: Klebsiella pneumoniae (K. pneumoniae) is a leading cause of serious hospital-acquired and community-acquired infections, with limited treatment options, especially for immunocompromised and critically ill patients. No licensed vaccine is currently available. The FimA antigen, a key fimbrial subunit essential for bacterial adhesion and invasion, represents a promising vaccine target. However, little is known about the immunodominant antibody responses against invasive K. pneumoniae. This study aimed to evaluate the immunogenicity and protective efficacy of recombinant FimA protein, to fine-map its immunodominant linear B-cell epitopes, and to assess the individual and combined protective capacity of these epitopes against both standard and clinically isolated K. pneumoniae strains. Methods: A murine model of lethal K. pneumoniae challenge was used. Recombinant FimA protein was administered to evaluate immunogenicity and protective efficacy. Immunodominant linear B-cell epitopes were identified by overlapping peptide ELISA using immune antisera. The identified epitopes were synthesized and conjugated to keyhole limpet hemocyanin (KLH). Mice were immunized with individual epitope-KLH conjugates or a mixture of all four, then challenged with the standard strain ATCC700721 or with multiple clinical isolates of distinct multilocus sequence types (MLST). Epitope-specific antibody responses (total IgG and IgG subclasses) and survival rates were measured. Results: Immunization with full-length recombinant FimA conferred 90% protection against lethal challenge with the standard strain ATCC700721 and induced robust IgG1-dominant antibody responses. Four novel immunodominant linear B-cell epitopes were identified: FimA_97–114, FimA_103–120, FimA_109–126, and FimA_145–160. Structural mapping revealed that the first three epitopes reside within the α-helical region, while FimA_145–160 is located in the β-sheet domain. These epitopes are highly conserved, exhibiting 100% sequence identity across 36 diverse K. pneumoniae strains. Among individual epitope-KLH conjugates, FimA_109–126-KLH induced the highest epitope-specific antibody titers, followed by FimA_103–120-KLH. Immunization with a mixture of all four epitope-KLH conjugates elicited significant cross-protection against multiple clinical isolates, achieving survival rates of 60%, 50%, 50%, and 40% against strains 10CYZ, 13LGY, 19ZXQ, and 22CZY, respectively. Protective immunity was primarily associated with IgG1 subtype responses. Conclusions: This study provides the first fine-mapping and protective evaluation of immunodominant linear B-cell epitopes within K. pneumoniae FimA. The identification of highly conserved, functionally relevant B-cell epitopes and the demonstration of cross-protection conferred by a multi-epitope formulation underscore the potential of FimA-based epitope-driven vaccines. These findings offer a promising strategy for the development of broadly protective vaccines against K. pneumoniae infections. Full article

S. suis is a major zoonotic infectious disease whose serological diversity brings challenges to vaccine development. Based on the whole-genome data of 169 S. suis strains, this study conducted a systematic bioinformatics analysis of the surface antigen protein HP0197 that reveals its distribution characteristics, sequence diversity, domain composition and antigenic epitope distribution. The results showed that the HP0197 gene, which has a detection rate of 91.72%, can be divided into seven major phylogroups (I–VII) and the following two structural types: short form (HP0197-S) and long form (HP0197-L). All sequences contained signal peptides, transmembrane structures, LPXTG anchoring motifs, as well as conserved GAGBD and G5 domains, among which tandem repeats of the G5 domain existed in the long HP0197-L type. Tertiary structure prediction indicated that HP0197 has a spatial architecture of “conserved at both ends and flexible in the middle”, in which B-cell epitopes are mainly enriched near the GAGBD and G5 domains, suggesting these regions are the key targets for inducing cross-immune protection. It systematically elucidates the diversity and structural characteristics of the HP0197 protein from the perspective of population genetics, which provides a theoretical basis for optimizing existing subunit vaccines, designing broad-spectrum multi-epitope vaccines and exploring novel anti-infection strategies. Full article