Modeling HIV vaccine trials of the future

Models of implementation of known-effective interventions for HIV prevention indicate that an efficacious vaccine to prevent HIV infection would be critical for controlling the HIV pandemic. Key issues in the design of future HIV vaccine trials are: first, how to develop reliable immunological correlates of vaccine efficacy, second, how to down-select candidate vaccine regimens into efficacy trials, and third, how to learn about vaccine efficacy in the context of the evolving HIV prevention landscape.

Whereas in the past phase-I/-II HIV vaccine trials have addressed the first and second points using a small set of immunological assays and readouts, recently they have used a battery of assays with highly multivariate readouts. In addition, systems vaccinology studies of other pathogens measuring PBMC transcriptomics and other immunological features pre- and postfirst vaccination are demonstrating value, for example, providing discoveries that preimmunization and early postimmunization cell population markers can predict the influenza-specific antibody titer that is a correlate of vaccine protection. The HIV prevention landscape continues to evolve, and the design and analysis of vaccine trials is evolving alongside, to accommodate increasingly dynamic and regional standards of HIV prevention.

Development of interpretable and robust functional assays, in addition to the associated bioinformatics and statistical analytic tools, is needed to improve the assessment of correlates of protection in efficacy trials and the down-selection of candidate vaccine regimens into efficacy trials. Moreover, high-priority trials should integrate systems vaccinology, including the analysis of prevaccination and early postvaccination markers.