Identification of immune response combinations associated with heterogeneous infection risk in the immune correlates analysis of hiv vaccine studies

In HIV vaccine/prevention research, probing into the vaccine-induced immune responses that can help to predict the risk of HIV infection provides valuable information for the development of vaccine regimens. Previous cor-relate analysis of the Thai vaccine trial aided the discovery of interesting immune correlates related to the risk of developing an HIV infection. The present study aimed to identify the combinations of immune responses asso-ciated with the heterogeneous infection risk. We explored a "change-plane" via combination of a subset of immune responses that could help separate vaccine recipients into two heterogeneous subgroups in terms of the associ-ation between immune responses and the risk of developing infection. Addi-tionally, we developed a new variable selection algorithm through a penalized likelihood approach to investigate a parsimonious marker combination for the change-plane. The resulting marker combinations can serve as candidate cor-relates of protection and can be used for predicting the protective effect of the vaccine against HIV infection. The application of the proposed statistical ap-proach to the Thai trial has been presented, wherein the marker combinations were explored among several immune responses and antigens.