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A major focus of the Mucosal Immunology laboratory is to unpack the correlates of risk or protection to HIV in the female genital tracts of participants from the various clinical trial and cohort follow-up studies that tested various HIV prevention modalities. These include the landmark CAP004 1% tenofovir gel trial, the first in human safety trial testing a subtype C derived broadly neutralizing antibody- CAP256V2LS in combination with VRC07-523LS and oral formulations of pre-exposure prophylaxis such as Truvada in the CAP082 and CAP084 studies. Here we focus on the immunological characteristics of B-cell responses such as antibodies and T cell- responses such as the immune cell activation and consequences of immune cell activation such as genital inflammation. A core of many immunological studies has been both the identification of genital inflammation as a key risk factor for HIV acquisition and testing the robustness of genital inflammation from the various clinical trials as a factor that undermines various formulations of PrEP.
Microbiome Research
The major focus of this core programme is to understand how microbes can perturb the vaginal microbiome environment from an optimal and healthy state to that of sub-optimal or dysbiotic state. Recently, there is increasing evidence of the role in microbial dysbiosis defined as a shift from a less diverse and Lactobacillus dominant vagina to that of a more diverse microbial environment that includes a dominance of non- Lactobacillus spp in fueling genital inflammation.- Importantly, through Dr Sinaye Ngcapu’s microbiome research programme, his group discovered stably colonized participants with Lactobacillus crispatus , and these isolates that were subsequently included in a clinical trial of a live biotherapeutic (LBP) product that was funded by the Bill and Melinda Gates Foundation. This LBP trial is currently ongoing and results are anticipated in June 2025. Besides this major advancement, Dr Ngcapu’s group is also invested heavily into understanding the mechanisms behind persistent bacterial vaginosis and the drivers of metronidazole resistant BV. In addition, this group intends on exploring various BV isolates through in vitro assays including the organ on chip, how a phage may be able to “rewire” the dysbiotic state of the vaginal microbial environment to that of a healthy and optimal state.
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