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

• Published in: Vaccine Vol. 31; no. 36; pp. 3739 - 3746
• Main Authors: Van Braeckel, E, Desombere, I, Clement, F, Vandekerckhove, L, Verhofstede, C, Vogelaers, D, Leroux-Roels, G
• Format: Journal Article
• Language: English
• Published: 12.08.2013
• Subjects: Antiviral agents; Human immunodeficiency virus 1
• ISSN: 0264-410X

A recombinant fusion protein (F4) consisting of HIV-1 pi 7, p24, reverse transcriptase (RT) and Nef, adjuvanted with AS01, induced strong and broad CD4 super(+) T cell responses in healthy volunteers. Here we compare these vaccine-induced CD4 super(+) 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 greater than or equal to 7 years; CD4 super(+) T cells greater than or equal to 500/ mu L), 10 recently infected individuals (infection less than or equal to 2 years; CD4 super(+) T cells greater than or equal to 500/ mu L), 10 typical early progressors (CD4 super(+) T cells mu 350/ mu L), and 10 viral controllers (plasma HIV-1 RNA <1000 copies/mL). Peripheral blood mononuclear cells were stimulated in vitro with pi7, p24, RT and Nef peptide pools and analyzed by flow cytometry for expression of IL-2, IFN- gamma , TNF- alpha and CD40L CD4 super(+) 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 super(+) T cells co-expressing IL-2, IFN- gamma and TNF- 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 super(+) T cells in vaccinees also expressed CD40L Subjects who spontaneously control an HIV infection display polyfunctional CD4 super(+) T cell responses to pi 7, p24, RT and Nef, with similar magnitude and qualities as those induced in healthy volunteers by an adjuvanted HIV candidate vaccine (F4/AS01).