title: 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).
authors.affiliation: Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Van Braeckel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desombere
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clement
authors.forename: Linos
authors.initials: L
authors.lastname: Vandekerckhove
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
authors.forename: Dirk
authors.initials: D
authors.lastname: Vogelaers
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015497:HIV-1; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D015488:HIV Antigens; D016655:HIV Core Protein p24; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D007371:Interferon-gamma; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
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