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 <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-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).