HIV therapeutic vaccine enhances non-exhausted CD4+ T cells in a randomised phase 2 trial

Abstract

VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4 + T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/μL. Participants were immunised with 16, 32, or 64 μg of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients ( p < 0.0001), compared to placebo. In high responders, the robust increased of CD4 count was associated with a significant and sustained reduction of PD-1 expression on CD4 + T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs ( p = 0.0092, r = −0.68) and expression of NKp44L ( p < 0.0001; r = 0.54) in CD4 + T cells. Our findings regarding the increase of non-exhausted CD4 + T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function.

Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients

“…The antigenicity of 3S or EC26 has been previously studied in French and German HIV-1 infected individuals and their immunogenicity has been tested in mice, nonhuman primates and humans 18 , 19 , 23 – 26 , 31 – 33 . Based on these results EC26 and, in particular, 3S are considered promising potential vaccine candidates 19 , 24 . However, these gp41 regions vary significantly between and within HIV-1 clades which may affect their antigenicity and immunogenicity 28 , 34 .…”

“…The 15-mer 3S peptide (aa 609–623) is located between heptad repeat 1 (HR1) and HR2, and contains the epitope 613-SWSNKS-618 21 – 24 . A single W-to-A substitution at position 614 originated peptide W164A-3S; anti-W164A-3S antibodies with neutralizing activity and conferring protection from CD4 + T cells depletion were detected in the sera of some HIV-1 patients 25 .…”

“…The immunogenicity of W164A-3S was tested in mice eliciting the production of broadly neutralizing antibodies 25 . More recently, in a therapeutic HIV-1 vaccine phase I / IIa clinical trial, W164A-3S increased the number of CD4 + T cells with a non-exhausted phenotype 24 .…”

Vaccine against COVID-19 or against SARS-CoV-2 infection?

“…Wyjątek stanowią np. HIV albo choroby nowotworowe [88,89]. Beneficjenci szczepionek nie staną w marszu naprzeciw tych, którzy uważają się za ofiary szczepień.…”

Peptide-Based Vaccination for Antibody Responses Against HIV

“…From these data, the VAC-3S therapeutic vaccine was developed, comprising the 3S peptide coupled with the CRM197 carrier protein formulated in an aluminum salt adjuvant (licenced by Minka Therapeutics). Moreover, a multi-center phase 2, randomized, double-blind, placebo-controlled clinical study revealed that VAC-3S is safe, immunogenic, and associated in high responders with an increase in non-exhausted CD4 + T cells [58].…”