Grant: Fellowship - PA: HIV/AIDS CHVI Vaccine Discovery and Social Research

Significance, Hypothesis HIV/AIDs is a major disease infecting 34 million individuals worldwide, and the number of infected people continue to rise in Canada, leading to a serious burden in high-risk populations. The development of a HIV vaccine requires global effort and is important to the control of spread of the virus. However, vaccination efforts are complicated by the fact that the human immune system is unable to trigger an protective response against HIV, because viruses mutate rapidly during an infection, allowing them to escape antibody neutralization. Broadly neutralizing antibodies (BNAbs) are more robust to viral mutation and neutralization escape. Therefore, promoting the immune system to produce BNAbs is a key strategy to developing an effective HIV vaccine. Research Plan As a CIHR fellow, I plan to develop statistical methods that are necessary to gain better understanding of the potency and breadth of BNAbs to neutralize HIV strains. The study will be based on HIV neutralization profiles generated from extensive wet-lab experiments by collaborators at the HIV Vaccine Trials Network based at the Fred Hutchinson Cancer Research Center. To appropriately analyze this complex high-dimensional data, we propose to use 'antigenic cartography' to model neutralization of virus-antibody pairs, which has already proved exceptionally useful to understanding cross-protective relationships among influenza strains. By providing a rigorous statistical foundation to the analysis of the HIV data, we can quantify neutralization ability of monoclonal antibodies (MAbs) to suggesting optimal targets for vaccine research and identify the additional benefit of using a combination of MAbs. While our project focuses on HIV/AIDs, these statistical methods can also be used to help improve the selection of vaccine strain in numerous other antigenically variable pathogens, including influenza and dengue viruses.