Systems serology: profiling vaccine induced humoral immunity against HIV

Amy W. Chung, Galit Alter

The results of the RV144 HIV vaccine, in combination with several recent non-human primate vaccine studies continue to highlight the potentially protective role of non-neutralizing Fc functional antibodies in HIV vaccine design. For many currently licensed vaccines, assays that detect antigen-specific antibody titers or neutralization levels have been used as a correlate of protection. However, antibodies can confer protection through multiple other mechanisms beyond neutralization, or mechanisms which are not dependent on total antibody titers. Alternative strategies that allow us to further understand the precise mechanisms by which antibodies confer protection against HIV and other infectious pathogens is vitally important for the development of future vaccines. Systems serology aims to comprehensively survey a diverse array of antibody features and functions, in order to simultaneously examine the mechanisms behind and distinguish the most important antibody features required for protection, thus identifying key targets for future experimental vaccine testing. This review will focus on the technical aspects required for the application of Systems serology and summarizes the recent advances provided by application of this systemic analytical approach.