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. 2024 Aug 28;24(1):873.
doi: 10.1186/s12879-024-09775-2.

Reverse vaccinology approaches to design a potent multiepitope vaccine against the HIV whole genome: immunoinformatic, bioinformatics, and molecular dynamics approaches

Ava Hashempour  1 , Nastaran Khodadad  2 , Shokufeh Akbarinia  1 , Farzane Ghasabi  1 , Younes Ghasemi  3   4 , Mohamad Matin Karbalaei Ali Nazar  1 , Shahab Falahi  5   6
Affiliations

Reverse vaccinology approaches to design a potent multiepitope vaccine against the HIV whole genome: immunoinformatic, bioinformatics, and molecular dynamics approaches

Ava Hashempour et al. BMC Infect Dis. .

Erratum in

Abstract

Substantial advances have been made in the development of promising HIV vaccines to eliminate HIV-1 infection. For the first time, one hundred of the most submitted HIV subtypes and CRFs were retrieved from the LANL database, and the consensus sequences of the eleven HIV proteins were obtained to design vaccines for human and mouse hosts. By using various servers and filters, highly qualified B-cell epitopes, as well as HTL and CD8 + epitopes that were common between mouse and human alleles and were also located in the conserved domains of HIV proteins, were considered in the vaccine constructs. With 90% coverage worldwide, the human vaccine model covers a diverse allelic population, making it widely available. Codon optimization and in silico cloning in prokaryotic and eukaryotic vectors guarantee high expression of the vaccine models in human and E. coli hosts. Molecular dynamics confirmed the stable interaction of the vaccine constructs with TLR3, TLR4, and TLR9, leading to a substantial immunogenic response to the designed vaccine. Vaccine models effectively target the humoral and cellular immune systems in humans and mice; however, experimental validation is needed to confirm these findings in silico.

Keywords: HIV; Bioinformatic; Main HIV subtypes and CRF; Molecular dynamic; TLR; Vaccine.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the flowchart of multiepitope vaccine design in this study
Fig. 2
Fig. 2
Percentage of the combined coverage of the selected CTL and HTL epitopes. A) Global population; B) dense population
Fig. 3
Fig. 3
Graphical map, tertiary structure, and ligand‒receptor docked complex of the HIV-vaccine construct. A) The vaccine constructs consisted of an adjuvant, as well as CTL, HTL, and BCL epitopes, arranged from left to right; B) Model-1 was constructed with I-TASEER software (protein modeling service) after refinement with the Galaxy Web server; C) Docked complex of the vaccine construct with C1) TLR-3, C2) TLR-4, and C3) TLR-9. The vaccine molecule is indicated in yellow, while TLR-3, TLR-4, and TLR-9 are indicated in blue. The lowest energy scores of the vaccine construct with other TLRs were − 1284.4 for TLR3, -1381.5 for TLR4, and − 1355.9 for TLR, according to the ClusPro server
Fig. 4
Fig. 4
RNAfold results and the mapping of discontinuous B-cell epitopes on HIV vaccine constructs. (A) mRNA secondary structures in the human model (A1-2) and mouse model (A3-4). In general, the red color in the RNAfold software secondary structure figure usually denotes the highest probability of RNA base pairing, and the colors shifting from orange, yellow, green, blue, and violet to pink represent the probability of a reduction in base pairing within the secondary structure of the vaccine. (B) Mapping of discontinuous B-cell epitopes on the vaccine construct (a-f) is shown by the yellow region of the vaccine, which displays each discontinuous B-cell epitope containing residues 3 to 84 with score values ranging from 0.536 to 0.771
Fig. 5
Fig. 5
MD analysis of the TLR-3, TLR-4, and TLR-9 vaccine constructs. A) The RMSD of the docked complex exhibits a small deviation, reflecting the stable interaction between the vaccine construct and TLRs. B) The RMSF plot remained flat, reflecting the flexibility of the side chain of the docked protein complex. C) The radius of the gyration plot reveals a relatively flat curve, indicating the presence of a stable vaccine-TLR complex. In the plots, TLR3, TLR4, and TLR9 are indicated with blue, orange, and gray, respectively
Fig. 6
Fig. 6
The immune simulation results obtained from C-IMMSIM after administering the vaccine construct were as follows: (a) The vaccine construct and immunocomplex trigger the production of various types of immunoglobulins. (b) Noticeable increase in the population of B cells, (c) significantly elevated population of active Th cells per state, (d) increased population of total Th cells, (d) increased population of active T cytotoxic lymphocytes per state, (f) elevated in the T cytotoxic (TC) cell population, and (g) elevated concentrations of cytokines and ILs. The inset plot shows the presence of a danger signal and the production of a substantial amount of the leukocyte growth factor IL-2
Fig. 7
Fig. 7
In silico cloning of the A) pET28 (a) plasmid and B) pAdTrack-CMV vector
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