Pathogen Genomics, Phenotype and Immunity (PGPI) & Basic Sciences Programme

Lead Research Organisation: London Sch of Hygiene and Trop Medicine

Abstract

This programme aims to conduct research that will lead to better understanding of pathogen genomics in order to characterise diseases and epidemics for better control and to investigate virological, immunological and genetic factors required for the development of effective interventions against HIV-1 and other infections. Advantage will be taken of a) well characterised cohorts and biobanks b) Unit track record in intervention trials c) investment in new technologies in genomics, immunological assays and bioinformatics and d) established collaborations.
We propose to monitor the HIV epidemic by characterising the circulating HIV-1 subtypes especially in recent infections and use full length genome sequencing to understand better the increasing recombinant viruses using better bioinformatics tools. We will use molecular in combination with social-epidemiological and modelling approaches to provide novel avenues to monitor epidemic trends and transmission dynamics, and to contribute to targeted interventions through the identification of transmission clusters and hotspots. HIV drug resistance (HIVDR) is emerging as one of the most important challenges to ART roll out for both care and prevention, more so in resource limited areas characterized by the use of limited ARV regimens, stock outs, regimen change based on available supply and often limited use of viral load (VL) testing to monitor treatment outcomes. We will expand our drug resistance studies to contribute to improved interventions.
HIV superinfection (SI) investigations will utilise a large collection of specimens from high risk populations to study host and viral factors associated with SI.

Technical Summary

We propose to monitor the HIV epidemic by characterising the circulating HIV-1 subtypes especially in recent infections and use full length genome sequencing to understand better the increasing recombinant viruses using better bioinformatics tools. We will use molecular in combination with social-epidemiological and modelling approaches to provide novel avenues to monitor epidemic trends and transmission dynamics, and to contribute to targeted interventions through the identification of transmission clusters and hotspots. We will expand our drug resistance (DR) studies to contribute to improved interventions. We are well positioned to provide such data being a National and Regional Reference laboratory for HIV DR and active participants in related national activities. We propose to undertake a comprehensive and systematic analysis of HIV-1 viruses representing the subtypes and recombinant forms circulating in Uganda to elucidate if transmitted/early HIV-1 viruses have recurrent patterns (signatures) that distinguish them from chronic viruses.
We will contribute to the studies aimed at understanding whether Zika virus exists among humans, primates and mosquitos in Uganda and conduct studies to molecularly characterize the Zika genome. There is renewed global interest in understanding events surrounding HIV superinfection (SI). However, due to the introduction of test and treat, opportunities to study this phenomenon are very limited. We are uniquely positioned to address this subject, we have a large collection of specimens from high risk populations and hence propose to investigate the host and viral factors associated with SI. This information will contribute to knowledge on protective immune responses. We recently won an NIH RO1 to address this topic and have set up an international collaborative network to address specific questions. The best vaccine induced protection achieved to date against SIV in macaques has been a live attenuated SIV. We propose to study the potential protective immune responses against HIV through PrEP in highly exposed populations. This is in order to explore whether exposure to HIV under PrEP cover could induce immunity equivalent to that afforded by a live attenuated vaccine. This is a proof of the concept that immunity to HIV might be achieved if the initial infections are hampered by chemoprophylaxis, simulating vaccination with a live attenuated virus strain. Gilead has provided the drugs for this study. We will participate in other studies to contribute to HIV Vaccine research and development

Publications

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