Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection

Abstract

Authorship note: HL, RWO, and BL contributed equally to this work. FAP is deceased. Conflict of interest: ML is the inventor of patents owned by Her Majesty The Queen In Right of Canada as represented by The Minister of Health: Canada patent no. 2,833,425, "Protease cleavage site peptides as an HIV vaccine"; US patent no. 10,285,942, "Methods of inducing an immune response against HIV by administering immunogenic peptides obtained from protease cleavage sites"; and European patent no. 2,694,654, "Protease cleavage site peptides as an HIV vaccine."

Natural Immunity against HIV-1: Progression of Understanding after Association Studies

“…After immunizations with the PCS vaccine, female MCMs were challenged repeatedly with pathogenic SIVmac251 by the intravaginal route. The data of the study showed for the first time that a vaccine targeting sequences surrounding PCS provided significant protection against repeated pathogenic SIVmac251 intravaginal challenges [84]. Notably, the PCS vaccine protected the monkeys without full-length Gag and Env immunogens.…”

“…With funding from NIH's "Innovation for HIV Vaccine Discovery" program and CIHR bridge fund, we tested the PCS vaccine approach in a nonhuman primate/SIV model [84]. Our preclinical studies demonstrated that an SIV vaccine targeting the sequences surrounding the 12 PCSs is protective.…”

“…All seven immune correlates of protection are T cells. These include RANTES, MIP-1α and IL-6 secreted by PBMCs after PCS peptide stimulation at the peak time point (week 73), and the frequency of the PCS peptide-specific Treg effector memory cell population at the pre-challenge time point (week 90) [84]. In addition, without antigen stimulation, the frequency of CCR5 expressing Th17 TEM cells and the frequency and intensity of CCR5 expressing CD8+IL17A+ TEM cells are also correlated with vaccine efficacy [84].…”

“…These include RANTES, MIP-1α and IL-6 secreted by PBMCs after PCS peptide stimulation at the peak time point (week 73), and the frequency of the PCS peptide-specific Treg effector memory cell population at the pre-challenge time point (week 90) [84]. In addition, without antigen stimulation, the frequency of CCR5 expressing Th17 TEM cells and the frequency and intensity of CCR5 expressing CD8+IL17A+ TEM cells are also correlated with vaccine efficacy [84]. The effect of PCS peptide-specific T cell responses on vaccine efficacy was clearly shown by a multiple regression analysis of the immunological data using LASSO [84].…”

“…In addition, without antigen stimulation, the frequency of CCR5 expressing Th17 TEM cells and the frequency and intensity of CCR5 expressing CD8+IL17A+ TEM cells are also correlated with vaccine efficacy [84]. The effect of PCS peptide-specific T cell responses on vaccine efficacy was clearly shown by a multiple regression analysis of the immunological data using LASSO [84]. The LASSO regression model identified six predictors that accurately predicted vaccine efficacy.…”