Aug 2026· Frontiers in Cellular and Infection Microbiology· Vol 16· 0 citations· 74 references
Medicine
TL;DR
The rationally designed multi-epitope vaccine demonstrates robust theoretical potential to elicit comprehensive, long-lasting immunity in humans, although its safety and effectiveness require additional experimental validation.
Abstract
Introduction Toxoplasma gondii is a significant zoonotic pathogen responsible for severe disease in immunocompromised individuals, adverse pregnancy outcomes, and substantial economic losses in the livestock industry. Given the limitations of current therapeutic strategies and vaccines, this study utilized immunoinformatics and reverse vaccinology approaches to design a multi-epitope candidate vaccine. Methods A total of 49 T. gondii proteins from the SAG, GRA, MIC, and ROP families were screened. Epitopes were selected based on antigenicity, immunogenicity, cytokine-inducing potential, toxicity, and allergenicity. The selected epitopes were assembled using AAY, GPGPG, and KK linkers, with the 50S ribosomal protein L7/L12 as an adjuvant. Physicochemical properties, molecular docking, molecular dynamics simulations, immune simulations, and codon optimization were subsequently evaluated. Results We identified 9 cytotoxic T lymphocyte (CTL), 6 helper T lymphocyte (HTL), and 11 B-cell epitopes. The finalized 556-amino-acid construct (61.13 kDa) demonstrated favorable antigenicity (VaxiJen score: 0.6843), stability (instability index: 39.05), solubility (0.663), and hydrophilicity (GRAVY: -0.502), while maintaining safety profiles. Molecular docking and dynamics simulations confirmed robust and stable binding to TLR2 (-32.8 kcal/mol) and TLR4 (-72.37 kcal/mol). Furthermore, immune simulations predicted a strong, memory-forming humoral and cellular immune response. Codon optimization (CAI: 0.93, GC content: 56.43%) suggested high expression efficiency in Escherichia coli. Discussion The rationally designed multi-epitope vaccine demonstrates robust theoretical potential to elicit comprehensive, long-lasting immunity in humans, although its safety and effectiveness require additional experimental validation.
Introduction Toxoplasma gondii can cause toxoplasmosis. It is an important type of pathogen within the broad category of emerging and re-emerging zoonoses. As an infectious disease featuring a complex multi-host transmission cycle, it poses an increasingly severe threat to global public health. No licensed vaccines are currently available for pets and humans, and thus a novel high-efficiency vaccine is urgently required. Methods Six antigens (GRA1, MIC17A, OWP2, LEA880, LEA870, and a hypothetical protein LEA530) representing different stages of the parasite lifecycle were selected from ToxoDB. T-cell and B-cell epitopes were predicted using immunoinformatics tools and screened based on antigenicity, allergenicity, and toxicity. The multi-epitope peptide (MEP1) was evaluated using molecular docking with Toll-like receptor 4 (TLR4) and immune simulation. The optimized sequence was expressed in HEK293T cells as a recombinant plasmid (MEP1-pcDNA3.1) and further evaluated in BALB/c mice. Results MEP1 contained 13 cytotoxic T lymphocyte epitopes, 16 helper T lymphocyte epitopes, and 12 B-cell epitopes, with a length of 732 amino acids and a predicted molecular weight of 75.73 kDa. The antigenicity score was 0.7343, and structural modeling indicated stable secondary and tertiary conformations. Molecular docking suggested strong binding affinity to TLR4. Immune simulation predicted increased B-cell and T-cell responses following vaccination. In vivo, MEP1-pcDNA3.1 immunization significantly increased serum IFN-γ levels (526.81 pg/mL) compared with PBS and pcDNA3.1 controls. Splenocyte proliferation was significantly enhanced in the MEP1-pcDNA3.1 group (SI = 1.58 ± 0.21) compared with PBS (1.10 ± 0.09) and pcDNA3.1 (1.12 ± 0.04) groups (P < 0.01). Following challenge with 5 × 10³ tachyzoites of the PLK strain, survival was markedly prolonged in vaccinated mice, whereas all control mice died within 2–4 days. Conclusion This study demonstrates an immunoinformatics-guided multi-epitope vaccine strategy against T. gondii, supported by in vivo immunogenicity and partial protective efficacy in a mouse model.
Wenyong Feng, Lu Sun, Chenglong Yang et al.· Frontiers in Immunology· 0 citations
Vc7 has been identified as a structurally stable and highly immunogenic construct, suggesting its potential as a universal multi-epitope vaccine candidate for the prevention of brucellosis.
Rhitam Biswas, Swapno Surabhi Sinha, Aditi Roy et al.· Frontiers in Bioinformatics· 0 citations
The Middle East is a significant hotspot for human hydatidosis caused by Echinococcus granulosus, a complex multi-stage pathogen exhibiting antigenic variation with diverse epitopes. Multi-epitope vaccines, designed using immunoinformatics, represent a promising approach to effectively control this challenging parasite. A total of 1150 secreted, non-toxic, antigenic proteins were obtained from database and analyzed for their immunogenic potential, leading to the identification of 1024 CTL, 80 HTL, and 172 LBL prioritized epitopes, which were then ranked and clustered to prefer the most immunogenicity epitopes to include in novel vaccine construct. The chosen Construct (Con2) was modified for dual-plasmid insertion, facilitating the expression of three different vaccine constructs which were predicted by C-ImmSim to stimulate robust IFN-γ/IL-2 production and enhance IgM/IgG antibody secretion. Utilizing in silico, next-generation vaccine design, we propose several vaccine candidates that warrant further validation through in vitro laboratory testing and in vivo studies to assess their immunological efficacy.
Dania Skhal, S. Al Nahhas, Osama Skhal et al.· Scientific Reports· 0 citations
The results highlight the potential of the proposed multi-epitope construct as a promising vaccine candidate against HCMV, however, experimental validation is essential to confirm its immunogenicity, safety, and translational applicability.
O. P. Emmanuel, M. N. Y. Sandrine, Bilanda Danielle Claude et al.· Scientific Reports· 0 citations
Computational findings suggest that the designed MESV is a promising vaccine candidate for MARV and warrants further experimental validation through in vitro and in vivo studies.
Asadullah Khan, Sitara Bibi, Pinyi Li et al.· Naunyn-Schmiedeberg's Archiv...· 0 citations
The computationally designed vaccine meets all essential criteria and has shown immense potential to be an effective vaccine through in silico analysis, however, additional In-vitro and In-vivo validations are imperative.
Swati Sharma, Prerna Verma, A. K. Keshri et al.· Discover Life· 0 citations
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