Long-Term Specific Immune Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine: Characterization of CD8⁺-T-Cell Epitopes Recognized

Abstract

We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone or with QS21 adjuvant to 28 HIV-uninfected volunteers. One month later, after a fourth injection of the vaccine, B-and T-cell anti-HIV responses were detected in >85% of the vaccinated volunteers. One year after this injection, a long-term immune response was observed in >50% of the volunteers. At this point, a positive QS21 effect was observed only in the sustained B-cell and CD4؉ -T-cell responses. To better characterize the CD8 ؉ -T-cell response, we used a gamma interferon enzyme-linked immunospot method and a bank of 59 HIV-1 epitopes. For the six most common HLA molecules (HLA-A2, -A3, -A11, -A24, -B7 superfamily, and -B8), an average of 10 (range, 3 to 15) HIV-1 epitopes were tested. CD8؉ -T-cell responses were evaluated according to the HLA class I molecules of the volunteers. Each assessment was based on 18 HIV-1 epitopes in average. We showed that 31 HIV-1 epitopes elicited specific CD8؉ -T-cell responses after vaccination. The most frequently recognized peptides were

Induction of Multifunctional Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T Cells Capable of Proliferation in Healthy Subjects by Using a Prime-Boost Regimen of DNA- and Modified Vaccinia Virus Ankara-Vectored Vaccines Expressing HIV-1 Gag Coupled to CD8+T-Cell Epitopes

“…Together these reports suggest that a protective T-cell response to HIV-1 infection may involve different subpopulations of multifunctional T cells (56). The implication for (11,14,23,41,51,52). Each study used different T-cell assays and applied different criteria to define the vaccine-induced T-cell response.…”

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

“…Previously tested HIV DNA vaccines have demonstrated excellent human safety profiles [4][5][6][7][8][9]. Recombinant protein-based HIV vaccines formulated with QS21 adjuvant have reported local reactions, but have shown limited systemic adverse events in humans [10][11][12][13][14][15]. The current report summarizes the phase 1 clinical safety and tolerability data, highlighting local and *Address correspondence to: Jeff Kennedy, M.D., Division of Molecular Medicine, Wadsworth Center, Biggs Laboratory, ESP, C606, NYS Department of Health, P.O.…”

De l’immunologie fondamentale au développement de la vaccinologie

“…Par exemple, dans l'essai de phase I, ANRS VAC 04, 28 volontaires sains ont reçu 3 injections de 6 lipopeptides dérivés des protéines Nef, Gag et Env du VIH et la tolérance a été bonne. On a constaté des réponses anticorps chez 90 % des sujets, et chez 80 % des sujets des réponses T CD4 ayant de multiples spécificités, ainsi que de nombreuses réponses T CD8 anti-Gag et anti-Nef de longue durée [24,25]. Dans les protocoles vaccinaux de l'ANRS engagés avec les lipopeptides, d'autres formulations ont été testées, incluant la présence de l'épi-tope auxiliaire de la toxine tétanique, ou un vecteur ALVAC, dérivé du Canari Pox.…”