Using samples collected longitudinally from HIV-1 infected subjects we are monitoring and characterizing the development of serum neutralizing antibody activities; focusing primarily on cross-neutralizing antibody activities. We are also investigating immunological and virological factors associated with the development of cross-neutralizing antibody responses, in the context of acute during chronic HIV-1 infection.
The goals of this grant are to express, purify and antigenically characterize trimeric gp140 clade C HIV envelope glycoproteins (derived from early HIV-1 infection) and to evaluate their immunogenic properties by serological and deep sequencing analyses.
We are specifically interested in optimizing the interaction of HIV envelope-based proteins with B cell receptors that give rise to specific broadly neutralizing HIV antibodies termed VRC01. This project involves extensive pre-clinical comparison of novel immunogens for future clinical testing.
The overall goal is 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.
This projects aims to determine the epitopes of the vaccine-elicited mabs on the near-native spike and determine whether the high resolution structures can help to move forward autologous neutralizing activity/specificity to increase breadth of elicited neutralization in support of the project goal to elicit broadly neutralizing antibodies to the human pathogen HIV-1.
The primary objective of the grant is to develop a second generation CSP-based malaria vaccine candidate. The aims of the subaward activities are to obtain structural information of protective and non-protective monoclonal antibodies isolated from humans against the P.falciparum circumsporozoite protein (PfCSP) in complex with their epitopes to determine critical and novel sites of vulnerability to inform immunogen design.