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

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-naive subjects were classified into four categories: 8 long-term non-progressors (infection >= 7 years; CD4(+) T cells >= 500/mu L), 10 recently infected individuals (infection <= 2 years; CD4(+) T cells >= 500/mu L), 10 typical early progressors (CD4(+) T cells <= 350/mu L), and 10 viral controllers (plasma HIV-1 RNA <1000 copies/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-gamma, TNF-alpha 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-gamma and TINF-alpha 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). (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.