V43DNA
Qualitative differences in the innate and adaptive responses elicited by different human immunodeficiency virus (HIV) vaccine candidates has not been thoroughly investigated. We tested the ability of Aventis Pasteur’s canarypox vector (ALVAC)–simian immunodeficiency virus (SIV), DNA–SIV and Ad26–SIV vaccine prime modalities together with two ALVAC–SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques in the V43DNA study (Nature Med., 2018). We found that the DNA and ALVAC prime (RV144-like, Nature Med., 2016) regimens were effective, but the Ad26 prime was not. Several datasets have been generated that quantify several parameters of immune mechanisms associated with the vaccine response (protection from infection after vaccination). These include transcriptomic data and cell phenotyping among others. The goal of this project was to generate an integrative model that combines all those available readouts in order to identify the mechanisms of action of the vaccines that lead to protection from infection. To that intent, we collected the different datasets available, verify the integrity of each dataset, reproduce published results and create an informatics system to easily access this data. An analytical approach (project-based regression model) was used to combining the datasets gathered while minimizing any bias specific to one readout.
The integrative model resulting from this approach identified the selective engagement of CD14+CD16− monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition.
We have used this integrated approach to identify correlates of protection to the Hep B vaccine (Nature Comm., 2016), biomarkers of sensibility/resistance to respiratory viruses (bioRxiv , 2018) and to the human HIV vaccine, RV144, that has shown limited efficacy (Nature Comm, under review)
This information is essential to the identification of biomarkers that predict protective vaccine responses, decipher the mechanism that allowed HV vaccine to confer protection against HIV acquisition and will ultimately allow the development of an improved vaccine against HIV.