Immune mechanisms underlying delayed disease progression in HIV-1 and HIV-2 infection

Lead Research Organisation: University of Oxford
Department Name: Clinical Medicine

Abstract

In order to design an effective vaccine against HIV infection we need to know more about how the immune system can combat HIV infection in people who have controlled the virus naturally without the need for drugs. We plan to study two groups of people where there are a large number of HIV-infected subjects who have low virus levels in their blood many years after being first infected, in China and West Africa.

Technical Summary

There remains an urgent need for an effective vaccine to prevent HIV infection. A key obstacle in vaccine design is the lack of understanding of the correlates of protective immunity against HIV infection. We propose to study potential correlates in two groups of HIV-infected subjects. The first is a plasma donor cohort in China, where infection of several hundred people appears to have occurred with a single virus strain. The second is a cohort in West Africa of HIV-2 infection, in which the majority of infected people are long-term non-progressors, but the minority who progress to disease do so in a manner identical to HIV-1 infection.

Publications

10 25 50

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De Silva T (2012) Effect of HIV-2 infection on HIV-1 disease progression. in The New England journal of medicine

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De Silva TI (2008) HIV-2: the forgotten AIDS virus. in Trends in microbiology

 
Description Li Ka Shing Foundation award for Oxford/China collaborations (PI Prof Jeremy Farrar)
Amount £50,000,000 (GBP)
Organisation Li Ka Shing Foundation 
Sector Charity/Non Profit
Country Hong Kong
Start 01/2007 
End 12/2009
 
Description UKRI-JSPS 2018 joint call: Structure-based vaccine design: using structural information from HIV-2 to design better HIV-1 immunogens
Amount £686,905 (GBP)
Funding ID MR/S020616/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2019 
End 02/2022
 
Title HIV sequences 
Description data on HIV-1 and HIV-2 sequences analysed in the Gambia have been added to the HIV database (Los Alamos) which is publicly available 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact none 
 
Title HIV-1 and HIV-2 sequences 
Description Sequences generated from patient samples collected in China and W. Africa. 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2009 
Provided To Others? Yes  
Impact Sequences submitted to the HIV database in Los Alamos and now publicly available. 
 
Title HIV-2 envelope clones 
Description Full length functional envelope clones generated from HIV-2-infected patients from W. Africa, used for neutralising antibody and other functional studies. 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact Studies of the ability of HIV-2 envelopes to antagonise tetherin are underway in Stuart Neil's lab (GKT). 
 
Title HIV-2 envelope clones 
Description these are full-length HIV-2 envelope clones from W. African patients used in neutralising antibody assays and other functional studies 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact work in progress in Stuart Neil's group for tetherin antagonism 
 
Title collection of blood samples from SM cohort in Henan, China 
Description DNA, plasma and cells have been collected and cryopreserved from a cohort of HIV-infected former plasma donors from Henan, China, and from a control cohort of HIV negative subjects from a nearby village. 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact Led to several high impact publications. 
 
Description Collaboration on TRIM5 alpha restriction of HIV-2 and other retroviruses 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint studies to identify novel polymorphisms in the TRIM 5 alpha gene and to determine their impact on the function of retroviral restriction
Collaborator Contribution Expertise in TRIM 5 alpha expression and functional studies
Impact joint funding proposal in preparation
Start Year 2011
 
Description HIV+ adolescents in Zimbabwe 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Our group is studying the immunology of a cohort recruited by investigators at the LSHTM
Collaborator Contribution Recruitment of the cohort, clinical and epidemiological expertise
Impact Joint grant applications Hosting Zimbabwean students in Oxford
Start Year 2011
 
Description Oxford/Gambia HIV-2 collaboration 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution Training of local technicians and students in the Gambia and during visits to Oxford for specialist research techniques.
Collaborator Contribution Provision of clinical and epidemiological data on long-term HIV-2 clinical and community cohorts, with sample bank. Access to selected samples for analysis. Hosting short-term visits of students and post-docs from our group in the Gambia, provision of access to laboratory facilities.
Impact Several joint publications. Successful completion of jointly supervised PhDs for MRC Gambia staff (Dr CO, Dr LMY).
 
Description Oxford/U. Washington HIV partnership 
Organisation University of Washington
Country United States 
Sector Academic/University 
PI Contribution We have provided training in cellular and molecular immunology techniques for Kenyan and US students, post-docs and technicians engaged in this collaboration and joint supervision of a PhD student (Jenn Slyker, completed PhD 2007).
Collaborator Contribution We have jointly applied for NIH funding (PI Dr Grace John-Stewart) and received an R01 award, of which approximately $400,000 was in the form of a subcontract from UW to our group (1999-2005). Our collaborators have provided clinical and epidemiological support to our research studies in Nairobi and we have jointly supervised a PhD student.
Impact Joint publications
 
Description Oxford/Youan collaboration on HIV infection 
Organisation Capital University of Medical Sciences
Department Youan Infectious Diseases Hospital
Country China 
Sector Academic/University 
PI Contribution Funding for sample collection and clinical laboratory tests (viral load, etc). Training of nominated clinician as PhD student in Oxford. Hosting short-term and longer-term visits by clinicians and laboratory researchers to Oxford for training in specialist techniques. Joint authorship of manuscripts.
Collaborator Contribution Arranging and coordinating sample collection, storage and shipment of samples collected from a chronic HIV-1 cohort in former plasma donors in Henan province, China. Access to laboratory facilities for short-term visitors from our research group. Provision of clinical and laboratory data about the cohort (anonymised)
Impact Dr YZ received his D. Phil. in 2009. Joint manuscripts have been submitted for publication. Regular collaborative visits from Beijing and Oxford researchers to the other centre.
 
Description Oxford Alumni weekend 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact I presented highlights of my research to the University of Oxford alumni weekend, under the title "Progress towards an HIV vaccine? lessons from Africa and China"

No major impacts
Year(s) Of Engagement Activity 2009
 
Description Oxford Students HIV day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact 50 people attended a multidisciplinary workshop on HIV research in Oxford at which I gave the keynote speech, leading to considerable discussion afterwards.

Links made with social science and public health researchers with an interest in HIV infection
Year(s) Of Engagement Activity 2011
 
Description Weatherall Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Talk to medical alumni of Oxford medical school about my research

Lively discussion
Year(s) Of Engagement Activity 2013
 
Description school visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Presentation on HIV vaccine research to around 25 intending science/medical students at local high school, which generated questions and discussion.

None reported
Year(s) Of Engagement Activity 2010