Polyfunctional CD4(+) T cell responses in HIV-1-infected viral controllers compared with those in healthy recipients of an adjuvanted polyprotein HIV-1 vaccine

Abstract

A recombinant fusion protein (F4) consisting of HIV-1 p17, p24, reverse transcriptase (RT) and Nef, adjuvanted with AS01, induced strong and broad CD4(+) T cell responses in healthy volunteers. Here we compare these vaccine-induced CD4(+) T cell responses with the ones induced by natural infection in patients with varying disease courses. Thirty-eight HIV-infected, antiretroviral treatment-naïve subjects were classified into four categories: 8 long-term non-progressors (infection ≥7 years; CD4(+) T cells ≥500/μL), 10 recently infected individuals (infection ≤2 years; CD4(+) T cells ≥500/μL), 10 typical early progressors (CD4(+) T cells ≤350/μL), and 10 viral controllers (plasma HIV-1 RNA <1000copies/mL). Peripheral blood mononuclear cells were stimulated in vitro with p17, p24, RT and Nef peptide pools and analyzed by flow cytometry for expression of IL-2, IFN-γ, TNF-α and CD40L. CD4(+) T cell responses were compared to those measured with the same method in 50 HIV-uninfected subjects immunized with the F4/AS01 candidate vaccine (NCT00434512). After in vitro stimulation with p17, p24 and RT antigen viral controllers had significantly more CD4(+) T cells co-expressing IL-2, IFN-γ and TNF-α than other HIV patient categories. The magnitude and quality of these responses in viral controllers were comparable to those observed in F4/AS01 vaccine recipients. In contrast with viral controllers, triple cytokine producing CD4(+) T cells in vaccinees also expressed CD40L. Subjects who spontaneously control an HIV infection display polyfunctional CD4(+) T cell responses to p17, p24, RT and Nef, with similar magnitude and qualities as those induced in healthy volunteers by an adjuvanted HIV candidate vaccine (F4/AS01).

Keywords: AIDS; AIDS Reference Center; ARC; ART; AS; CD4(+) T cell response; CD40-ligand; CD40L; F4; HCV; HIV; HIV-1; HIV-1 vaccine; IFN-γ; IL-2; LTNP; MSM; PBMC; RI; RT; TEP; TNF-α; VC; VU; Viral controllers; acquired immune deficiency syndrome; adjuvant system; antiretroviral therapy; gamma interferon; hepatitis C virus; human immunodeficiency virus; interleukin 2; long-term non-progressors; men-who-have-sex-with-men; peripheral blood mononuclear cells; recently infected individuals; recombinant fusion protein comprised of HIV-1 p17, p24, RT and Nef; reverse transcriptase; tumor necrosis factor alpha; typical early progressors; vaccinated uninfected individuals; viral controllers.