title: Early CD4+ T Cell Responses Are Associated with Subsequent CD8+ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|CHU de Bordeaux, Pôle de santé publique, Bordeaux, France.|INRIA SISTM, Talence, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Lhomme
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|CHU de Bordeaux, Pôle de santé publique, Bordeaux, France.|INRIA SISTM, Talence, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Richert
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States of America.|HIV Vaccine Trials Network, Seattle, Washington, 98109, United States of America.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|INRIA SISTM, Talence, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Pasin
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, United States of America.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States of America.|HIV Vaccine Trials Network, Seattle, Washington, 98109, United States of America.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States of America.|HIV Vaccine Trials Network, Seattle, Washington, 98109, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States of America.|HIV Vaccine Trials Network, Seattle, Washington, 98109, United States of America.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.|CHU de Bordeaux, Pôle de santé publique, Bordeaux, France.|INRIA SISTM, Talence, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004274:DNA, Recombinant / Q000276:immunology; D005822:Genetic Vectors / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008875:Middle Aged; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004274:DNA, Recombinant; D007376:Interleukin-2; D019444:Vaccines, DNA; D007371:Interferon-gamma