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Early CD4+ T Cell Responses Are Associated with Subsequent CD8+ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy.
Lhomme, Edouard; Richert, Laura; Moodie, Zoe; Pasin, Chloé; Kalams, Spyros A; Morgan, Cecilia; Self, Steve; De Rosa, Stephen C; Thiébaut, Rodolphe.
Afiliação
  • Lhomme E; INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
  • Richert L; Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
  • Moodie Z; CHU de Bordeaux, Pôle de santé publique, Bordeaux, France.
  • Pasin C; INRIA SISTM, Talence, France.
  • Kalams SA; Vaccine Research Institute (VRI), Créteil, France.
  • Morgan C; INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
  • Self S; Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
  • De Rosa SC; CHU de Bordeaux, Pôle de santé publique, Bordeaux, France.
  • Thiébaut R; INRIA SISTM, Talence, France.
PLoS One ; 11(4): e0152952, 2016.
Article em En | MEDLINE | ID: mdl-27124598
INTRODUCTION: Initial evaluation of a candidate vaccine against HIV includes an assessment of the vaccine's ability to generate immune responses. However, the dynamics of vaccine-induced immune responses are unclear. We hypothesized that the IFN-γ producing cytotoxic CD8+ (CD8+ IFN-γ+) T cell responses could be predicted by early IL-2 producing CD4+ (CD4+ IL-2+) helper T cell responses, and we evaluated this hypothesis using data from a phase I/II prophylactic HIV vaccine trial. The objective was to assess the dynamics and correlations between CD4+ IL-2+ T cell and CD8+ IFN-γ+ T cell responses after vaccination with a recombinant adenoviral serotype 5 (rAd5) HIV vaccine. METHODS: We analyzed data from the HVTN 068 HIV vaccine trial, which evaluated the immunogenicity of two different strategies for prime and boost vaccination (rAd5-rAd5 vaccine versus DNA-rAd5) in 66 healthy volunteers. Spearman correlations between immunogenicity markers across time-points were calculated. CD8+ IFN-γ+ T cell response in the rAd5-rAd5 arm was modeled as a function of CD4+ IL-2+ T cell response and time using mixed effects regression models. RESULTS: Moderate to high correlations (r = 0.48-0.76) were observed in the rAd5-rAd5 arm between the CD4+ IL-2+ T cell response at week 2 and later CD8+ IFN-γ+ T cell responses (weeks 2-52). Regression models confirmed this relationship with a significant association between the two markers: for a 1.0% increase in CD4+ IL-2+ T cells at week 2 post-prime, a 0.3% increase in CD8+ IFN-γ+ T cell responses across subsequent time points, including post-boost time points, was observed (p<0.01). CONCLUSION: These results suggest an early and leading role of CD4+ T cells in the cellular response to the rAd5-rAd5 vaccine and in particular the stimulation of cytotoxic CD8+ T cell responses. These results could inform better timing of CD4+ T cell measurements in future clinical trials.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 / Vacinas contra a AIDS / Linfócitos T CD8-Positivos Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Humans / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 / Vacinas contra a AIDS / Linfócitos T CD8-Positivos Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Humans / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: França