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. 2025 Mar;23(1):100451.
doi: 10.1016/j.jgeb.2024.100451. Epub 2024 Dec 16.

Multi-epitope-based vaccine models prioritization against Astrovirus MLB1 using immunoinformatics and reverse vaccinology approaches

Awais Ali  1 , Syed Luqman Ali  1 , Abdulaziz Alamri  2 , Elham Mohammed Khatrawi  3 , Aliya Baiduissenova  4 , Fatima Suleimenova  5 , Vipin Kumar Mishra  6 , Asifullah Khan  7 , Marat Dusmagambetov  8 , Gulsum Askarova  9
Affiliations

Multi-epitope-based vaccine models prioritization against Astrovirus MLB1 using immunoinformatics and reverse vaccinology approaches

Awais Ali et al. J Genet Eng Biotechnol. 2025 Mar.

Abstract

Astrovirus MLB1 (HAstV-MLB1) is non-enveloped RNA virus that cause acute gastroenteritis infection. Despite research progress about infection and pathogenesis of HAstV-MLB1, Currently, no vaccine has been developed to effectively combat this pathogen. The current study is based on immunoinformatics and reverse vaccinology approaches to design next-generation, multi-epitope-based vaccine models against HAstV-MLB1. Genome-wide whole proteome data of HAstV-MLB1 strain was retrieved, and a series of analyses were conducted to explore effective B and T-cell epitopes that hold significant antigenic nature with no toxicity and allergenicity VSports手机版. A set of vaccine constructs were designed by different combination of lead B and T-cell epitopes with diverse linkers and adjuvants sequences. The model vaccine structures were analyzed via rigorous criteria of physiochemical properties, antigenicity, and molecular docking with HLA and TLR4 immune receptors to ensure their efficacy and safety. Based on the lowest binding energy of -82. 48 kcal/mol against the HLA receptor, the MLB1-C2 vaccine model with β-definsin adjuvant was prioritized for molecular dynamic and immune simulations analyses to assess its stability and immunogenic potential. These analyses revealed that the MLB1-C2 construct has feasible molecular stability and potential to boost strong immune responses in the host cell. Besides, the model was predicted to be non-toxic, non-allergenic, and antigenic, ensuring broad population coverage and capable to elicit a robust immune response. The in-silico cloning analysis highlighted a possible gene expression potential of the MLB1-C2 construct in E. coli commercial recombinant vector molecule. The findings of the current study provide an essential template for the development of a advanced next-generation effective vaccine against HAstV-MLB1. .

Keywords: Acute gastroenteritis; Human Astrovirus MLB1; Immunoinformatics; Reverse vaccinology; Vaccine designing. V体育安卓版.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Methodological flow chart of the current study and strategies applied for the designing a multi-epitope vaccine designing against HAstV-MLB1 virus.
Fig. 2
Fig. 2
Population coverage evaluation of selected epitopes, (A) MHC-1 and MHC-2 epitope coverage for proteins across global regions. West- indies, East Asia, Europe, and South America show the highest overall coverage, (B) MHC-1 and MHC-2 epitope coverage for proteins across major continental ethnic groups.
Fig. 3
Fig. 3
A MEV construct with β-definsin adjuvant by combining B and T cells epitopes with appropriate linkers.
Fig. 4
Fig. 4
2D and 3D structure refinement and validation of MLB1-C2 (A) secondary structure of MLB1-C2 construct (B) the protein's overall quality, indicated by the Z-score of −1.2, (C) Tertiary structure energy map (D) ProSA-web plot showing residue scores in a native protein structure (E) Ramachandran analysis of model vaccine protein with 84.1% of residues in favored regions, 10.7% in the allowed region, 3.7% generously in allowed, and only 1.4 % in disallowed (1.4%) regions, indicating structural accuracy.
Fig. 5
Fig. 5
Significant molecular docking pose of lead anti-HAstV-MLB1 vaccine model (A) docked complex of MLB1-C2 with TLR4 (B) HADDOCK Cluster distribution for TLR4C2, showing the top 10 clusters. Cluster 4 exhibits the best HADDOCK score (−4.9 ± 3.8 kcal/mol) and a Z-score of −2.3, though with a higher RMSD (9.9 ± 0.1 Å) and significant restraints violation energy.
Fig. 6
Fig. 6
Molecular docking pose of lead anti-hastv-mlb1 vaccine model (a) docked complex of mlb1-c2 with hla (b) haddock cluster distribution for hlac2, showing the top 10 clusters. cluster 1 has the best haddock score (−6.2 ± 3.1 kcal/mol) and a Z-score of −2.5, indicating a reliable docking solution with low RMSD (3.5 ± 0.1 Å) and minimal restraints violation energy.
Fig. 7
Fig. 7
Significant structural flexibility of MLB1-C2-TLR4 complex showed during NMA analysis. The main chain deformability (A), quantified atom uncertainties with B-factor calculation (B) Deformability, the energy required to deform adjacent complexes. (C) Eigen values show a covariance matrix. (D) Residue correlations showing correlated (red), anti-correlated (blue), and uncorrelated (white) regions (E). The elastic network model demonstrated the interaction between springs and atoms, with darker grey denoting stiffer springs (F).
Fig. 8
Fig. 8
Time series of root mean square deviations (RMSD) for (A) HLA receptor with MLB1-C2, and (B) TLR4 receptor with MLB1-C2.
Fig. 9
Fig. 9
RMSF values for the (A) values for the MLB1-C2-HLA complex., and (B) MLB1-C2-TLR4 complex.
Fig. 10
Fig. 10
(a) The number of hydrogen bonds between the HLA receptor and the vaccine, (b) The Number of hydrogen bonds between TLR4 receptor and vaccine.
Fig. 11
Fig. 11
The C-ImmSim web-server was used to assess the immune responses to the lead MLB1-C2 vaccine construct, demonstrating dynamic immune changes over time. (A) After antigen stimulation, primary B-cell antibodies (IgM + IgG) increased, forming an essential barrier against infections. (B) Changes in the HTLs' secretion levels show a strong cellular immune response. (C) Increased secretion from active B cells further boosted the immune response. (D) Levels of CTL secretion increased, indicating successful targeting of infected cells. (E) An important finding was that levels of cytokine secretion, primarily IL-2 and IFN-γ, increased, demonstrating the vaccine's potential to activate critical immune mediators. (F) After the 3rd dose, B-cell count shows a remarkable increase, leading to a dynamic switch between various B-cell isotypes. This leads to a distinct accumulation of active plasma B cells producing both IgM and IgG antibodies). (G-H) a robust response is observed among the active phase T-cell population, showing higher concentrations compared to the anergic phase T-cellss (I) showing macrophage activation.
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V体育ios版 - References

    1. Kumthip K., Khamrin P., Ushijima H., Maneekarn N. Molecular epidemiology of classic, MLB and VA astroviruses isolated from< 5 year-old children with gastroenteritis in Thailand, 2011–2016. Infect Genet Evol. 2018;65:373–379. - PubMed
    1. Moser L.A., Schultz-Cherry S. Pathogenesis of astrovirus infection. Viral Immunol. 2005;18:4–10. - PubMed
    1. Wei H., Kumthip K., Khamrin P., et al. Triple intergenotype recombination of human astrovirus 5, human astrovirus 8, and human astrovirus 1 in the open reading frame 1a, open reading frame 1b, and open reading frame 2 regions of the human astrovirus genome. Microbiol Spectr. 2023 - "V体育官网入口" PMC - PubMed
    1. Holtz L.R., Bauer I.K., Jiang H., et al. Seroepidemiology of astrovirus MLB1. Clin Vaccine Immunol. 2014;21:908–911. - "V体育官网入口" PMC - PubMed
    1. Finkbeiner S.R., Kirkwood C.D., Wang D. Complete genome sequence of a highly divergent astrovirus isolated from a child with acute diarrhea. Virol J. 2008;5:1–7. - PMC - PubMed

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