Use of this data requires authorization from the National Institutes of Allergy and Infectious Diseases (NIAID), the NIAID Vaccine Study Center (VRC), and the HVTN. of the vaccines ability to generate immune reactions. However, the dynamics of vaccine-induced immune reactions are unclear. We hypothesized the IFN- generating cytotoxic CD8+ (CD8+ IFN-+) T cell reactions could be expected by early IL-2 generating CD4+ (CD4+ IL-2+) helper T cell reactions, and we evaluated this hypothesis using data from a phase I/II prophylactic HIV vaccine trial. The objective was to assess the dynamics GW 501516 and correlations between CD4+ IL-2+ T cell and CD8+ IFN-+ T cell reactions after vaccination having a recombinant adenoviral serotype 5 (rAd5) HIV vaccine. Methods We analyzed data from your HVTN 068 HIV vaccine trial, which evaluated the immunogenicity of two different strategies for perfect 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-+ T cell response in the rAd5-rAd5 arm was modeled like a function of CD4+ IL-2+ T cell response and time using mixed effects regression models. Results Moderate to high correlations (r = 0.48C0.76) were observed in the rAd5-rAd5 arm between the CD4+ IL-2+ T cell response at week 2 and later CD8+ IFN-+ T cell reactions (weeks 2C52). Regression models confirmed this relationship with a significant association between the two markers: for any 1.0% increase in CD4+ IL-2+ T cells at week 2 post-prime, a 0.3% increase in CD8+ IFN-+ T cell responses across subsequent time points, including post-boost time points, was observed (p 0.01). Summary These results suggest an early and leading part of CD4+ T cells in the cellular response to the rAd5-rAd5 vaccine and in particular the activation of cytotoxic CD8+ T cell reactions. These results could inform better timing of CD4+ T cell measurements in future medical tests. Introduction More than thirty years after the identification of the human being immunodeficiency disease (HIV) as the etiological agent of GW 501516 acquired immunodeficiency syndrome (AIDS), the global HIV epidemic remains one of the major global health difficulties [1,2]. The development of a safe and efficacious prophylactic vaccine strategy against HIV constitutes an opportunity to control the pandemic. Several clinical tests have been carried out in recent years to evaluate prophylactic strategies combining different candidate vaccines, but showed at best moderate effectiveness [3C8]. Earlier tests possess especially highlighted the importance of the vaccine routine, in particular the concept of perfect and boost strategy to optimize vaccine effectiveness [3,9,10]. Although correlates of safety in HIV vaccine tests are not yet validated, both cellular and humoral immune reactions are likely LRAT antibody required to accomplish adequate protecting vaccine effectiveness against HIV acquisition. The assessments of these immune reactions therefore play a major role in phase I-II HIV vaccine tests and in the decision to proceed to large scale effectiveness trials. One goal of vaccine-induced cellular reactions is definitely to stimulate CD8+ cytotoxic reactions able to efficiently fight against the virus and to control the infection. IL-2 producing CD4+ T cells play a role in the generation of this response, as they activate the differentiation of CD8+ cytotoxic effector cells and memory space cells. They also help for the differentiation of B cells. [11,12]. However, little is known about the human relationships between the different markers of immunologic response in HIV vaccine recipients, and little data are available within the dynamics of immunologic reactions over time. The time points at which different immunogenicity markers are measured in phase I and II HIV vaccine tests vary but are usually selected between two and four GW 501516 weeks after the final vaccine injection [13]. A better understanding of the dynamics of vaccine-induced immune reactions would help.