Ndung’u: Profiling Virus Neutralization in the KwaZulu-Natal FRESH Cohort
This grant will be used to enroll and longitudinally follow participants in the FRESH Program (Females Rising through Education Support and Health) based in KwaZulu-Natal, South Africa. In this program, women at high risk for HIV infection enter a socioeconomic empowerment curriculum that combines social good with basic science research into HIV acquisition and hyperacute infection. This investment will primarily be used to study virus sensitivity to broadly neutralizing antibodies (bNAbs) in the FRESH cohort. Efforts will focus on profiling recently identified transmitted/founder (T/F) and reservoir (lymph node)-derived viruses to identify the bNAb combinations likely to be most effective against circulating HIV-1 clade C viruses.
The specific goals of this investment are:
1) Enroll into the FRESH cohort and longitudinally follow approximately 300 women (aged 18-24) at risk for HIV infection. Perform HIV RNA testing twice per week to identify hyperacute HIV infection cases, who will immediately be started on antiretroviral therapy.
2) Determine the sensitivity of 77 T/F and 20 reservoir viruses to bNAbs targeting the 5 major known epitopes of the Env glycoprotein.
3) Identify combinations of bNAbs with great breadth and potency as candidate immunoprophylactic agents against contemporaneous circulating clade C viruses.
4) Determine the genotypic and neutralization properties of T/F viruses and reservoir viruses to identify how viral diversity impacts antibody recognition.
By identifying the best individual or combinations of bNAbs that can block T/F and reservoir (lymph node)- derived circulating HIV-1 subtype C, these studies aim to inform immunoprophylactic strategies in a highincidence setting.