Immunogenicity and Efficacy of a Novel Multi-Antigenic Peptide Vaccine Based on Cross-Reactivity between Feline and Human Immunodeficiency Viruses

Abstract

For the development of an effective HIV-1 vaccine, evolutionarily conserved epitopes between feline and human immunodeficiency viruses (FIV and HIV-1) were determined by analyzing overlapping peptides from retroviral genomes that induced both anti-FIV/HIV T cell-immunity in the peripheral blood mononuclear cells from the FIV-vaccinated cats and the HIV-infected humans. The conserved T-cell epitopes on p24 and reverse transcriptase were selected based on their robust FIV/HIV-specific CD8+ cytotoxic T lymphocyte (CTL), CD4+ CTL, and polyfunctional T-cell activities. Four such evolutionarily conserved epitopes were formulated into four multiple antigen peptides (MAPs), mixed with an adjuvant, to be tested as FIV vaccine in cats. The immunogenicity and protective efficacy were evaluated against a pathogenic FIV. More MAP/peptide-specific CD4+ than CD8+ T-cell responses were initially observed. By post-third vaccination, half of the MAP/peptide-specific CD8+ T-cell responses were higher or equivalent to those of CD4+ T-cell responses. Upon challenge, 15/19 (78.9%) vaccinated cats were protected, whereas 6/16 (37.5%) control cats remained uninfected, resulting in a protection rate of 66.3% preventable fraction (p = 0.0180). Thus, the selection method used to identify the protective FIV peptides should be useful in identifying protective HIV-1 peptides needed for a highly protective HIV-1 vaccine in humans.

Plant-made HIV vaccines and potential candidates

“…Increases in CD4 + and CD8 + T cell MAP responses were observed in nearly 80% of the cats, implying protection against FIV [41]. This criterion can be similarly applied in humans to select for protective HIV-1 peptides that can be used to formulate an effective vaccine against HIV-1.…”

“…Recently, evolutionarily conserved epitopes between Feline immunodeficiency virus (FIV) and HIV were explored as a means of developing an effective vaccine [41]. In this study, Sahay and colleagues identified overlapping peptides that elicited T cell immunity in HIV-infected people and FIV-vaccinated cats.…”

A comprehensive and critical overview of schistosomiasis vaccine candidates

“…2 ) (Tam 1988 ). Synthesizing peptides as MAP and peptide dendrimers can induce higher immune response and recently were used as a vaccine model against Plasmodium falciparum (Mahajan et al 2010 ), Yersinia pestis (Shreewastav et al 2012 ), filarial nematodes (Immanuel et al 2017 ), and human immunodeficiency viruses (HIV) (Sahay et al 2019 ). Besides, all required protective B and T cell epitopes can be included in one single MAP molecule (Fig.…”

A Multiple Antigen Peptide Vaccine Containing CD4+ T Cell Epitopes Enhances Humoral Immunity against Trichinella spiralis Infection in Mice

“…The branched peptides sometimes can greatly increase their immunological responses because of the high molar ratio of peptide antigen to the core molecule and the high molecular weight which make them more immunogenic without the need of conjugation to a carrier protein [32,[34][35][36]. MAP vaccines have been studied in several infectious diseases, such as lymphatic filariasis [37], Plasmodium falciparum (P. falciparum) [38], Yersinia pestis [39], and HIV [40]. Clinical studies have been carried out in MAP vaccine against P. falciparum sporozoites [41].…”