Immune responses to HIV

Africa bears the largest burden of infections, and human response influences the general health of the population, when some people have better disease outcomes. By working within our context, we can identify relevant targets for vaccine development, and also understand the immune response we can expect when implementing an intervention.

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I am a research scientist based at the KEMRI Wellcome Trust Research Programme (KWTRP), Kilifi Kenya. I currently hold a Mid-Level-Career fellowship under the Wellcome Trust funded KWTRP/IDEAL Programme and have additional support from the International AIDS Vaccine Initiative (IAVI) to study various aspects of HIV immunology and pathogenesis.

My primary focus is to understand the cellular and molecular mechanisms involved in the generation of antibodies with relevant functions. Specifically, I am interested in understanding B and T follicular helper (Tfh) cell interactions and how these may impact on the quality of the subsequent HIV-specific antibodies produced. The generation of broadly neutralizing antibodies requires many rounds of affinity maturation, an event that occurs in the germinal centre and requires help from Tfh cells, which play a critical role in the formation of germinal centers and providing important signals to B cells. It is therefore reasonable to suggest that the quality of the Tfh cells activated can determine success or failure in the generation of broadly neutralizing antibodies, or antibodies with other protective functions.  Understanding the interaction of Tfh cells with B cells therefore remains relevant for the development of antibody-based vaccines. While antibody neutralization breadth takes time to develop, antibodies with other Fc mediated functions appear early in HIV infection and I am also interested in understanding their potential role in early viral control.

As part of our collaborative programme with IAVI, I am interested in establishing immunogenicity testing frameworks for HIV vaccine studies. This involves establishing and coordinating high-risk adult population cohorts and setting up relevant functional assays for both humoral (neutralizing and Fc mediated antibody functional assays) and CD8 mediated function (Viral Inhibition Assays and Interferon gamma ELISPOT). This framework has contributed to HIV prevention and care programming for key populations in Kenya and towards our understanding of host immune responses in the context of natural HIV infection.