Dr. Zaza Ndhlovu

This funding will support the design of a T cell-based HIV vaccine that will be effective in sub-Saharan Africa. Durable control of viremia is associated with CTL targeting of highly networked, mutationally intolerant epitopes called highly networked epitopes, but it is unclear if the highly networked epitopes identified in clade B are conserved across HIV subtypes. Moreover, HLA class I restriction of networked epitopes has not been determined, and little is known about allelic and HLA haplotype diversity in sub-Saharan African populations. Therefore, the goals of this project are 1) to determine whether highly networked epitopes identified in clade B are immunogenic in eastern and southern African individuals infected with clade A, C, D, and/or G or their inter-subtype recombinants; 2) to identify the class I HLA allele restriction associated with immune control of HIV for highly networked epitopes that are frequently recognized in eastern and southern Africa; 3) to investigate geographical heterogeneity in allele frequency and HLA supertype across eastern and southern Africa; and 4) to create a publicly available database of high-resolution HLA allele and haplotype frequencies in eastern and southern African populations. By characterizing HLA allele and haplotype frequencies and networked epitope combinations in eastern and southern Africa, this project will generate information regarding HLA usage that could inform the development of vaccines for a variety of pathogens, including HIV, HPV, and malaria.

This grant is led by Dr. Zaza Ndhlovu (AHRI), in collaboration with Drs. Thumbi Ndung’u (AHRI), Veron Ramsuran (University of KwaZulu-Natal), Etienne Karita (Rwanda Zambia HIV Research Group), Caroline Chisenga (Centre for Infectious Disease Research in Zambia), and Daniel Muema (KAVI-Institute of Clinical Research, University of Nairobi).