Design of multivalent-epitope vaccine models directed toward the world's population against HIV-Gag polyprotein: Reverse vaccinology and immunoinformatics

PLoS One. 2024 Sep 27;19(9):e0306559. doi: 10.1371/journal.pone.0306559. eCollection 2024.

Abstract

Significant progress has been made in HIV-1 research; however, researchers have not yet achieved the objective of eradicating HIV-1 infection. Accordingly, in this study, eucaryotic and procaryotic in silico vaccines were developed for HIV-Gag polyproteins from 100 major HIV subtypes and CRFs using immunoinformatic techniques to simulate immune responses in mice and humans. The epitopes located in the conserved domains of the Gag polyprotein were evaluated for allergenicity, antigenicity, immunogenicity, toxicity, homology, topology, and IFN-γ induction. Adjuvants, linkers, CTLs, HTLs, and BCL epitopes were incorporated into the vaccine models. Strong binding affinities were detected between HLA/MHC alleles, TLR-2, TLR-3, TLR-4, TLR-7, and TLR-9, and vaccine models. Immunological simulation showed that innate and adaptive immune cells elicited active and consistent responses. The human vaccine model was matched with approximately 93.91% of the human population. The strong binding of the vaccine to MHC/HLA and TLR molecules was confirmed through molecular dynamic stimulation. Codon optimization ensured the successful translation of the designed constructs into human cells and E. coli hosts. We believe that the HIV-1 Gag vaccine formulated in our research can reduce the challenges faced in developing an HIV-1 vaccine. Nevertheless, experimental verification is necessary to confirm the effectiveness of these vaccines in these models.

MeSH terms

  • AIDS Vaccines* / immunology
  • Animals
  • Computational Biology / methods
  • Epitopes / immunology
  • Epitopes, T-Lymphocyte / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1* / immunology
  • Humans
  • Immunoinformatics
  • Mice
  • Vaccinology / methods
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • gag Gene Products, Human Immunodeficiency Virus
  • Epitopes
  • Epitopes, T-Lymphocyte

Grants and funding

This project was funded by Shiraz University of Medical Sciences, Shiraz, Iran (grant number 29467). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.