Malaria and HIV/AIDS are two of the most devastating infectious diseases, impacting millions of people world- wide. Effective vaccines against the pathogens that cause these diseases (HIV and Plasmodium falciparum) have proven elusive and traditional vaccine approaches are unlikely to succeed in eradicating either disease. In addition to our limited understanding of the desired immune responses to confer protection against the pathogens and our limited ability to elicit such responses, vaccine efficacy is also confounded by the diversity of pathogens, human populations, environmental exposures, and health status. The projects described herein are designed to support the identification of immune profiles that correlate with vaccine efficacy and are of potential relevance to protection against HIV-1 and P. falciparum infection. Beyond the importance of combatting these diseases, the strategies for profiling immunity in response to infection and vaccination hold promise for garnering fundamental insights into the complexity of the immune system as a whole. Such insight will have potential for impacting strategies for vaccine development and for treating immune-related diseases more broadly.