Neutralizing antibody responses in HIV-2

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Natural infection with many viruses results in the production of antibodies which help clear the virus and protect us from subsequent reinfection. Eliciting such a response is the basis of many effective vaccines, but unfortunately little is understood about protective antibody responses in HIV, which has hindered HIV vaccine design. Despite sharing many similarities with HIV-1, most patients with HIV-2 do not develop AIDS (although a minority do) and the reasons for this are not entirely clear. This project proposes to compare neutralizing antibody responses in HIV-1 and HIV-2 infection and explore whether stronger responses are found in HIV-2 infected patients who do not progress to AIDS, when compared to HIV-2 progressors and HIV-1 patients.||Early studies also suggested that HIV-2 antibodies could render HIV-1 non-functional and although some previous studies claimed HIV-2 infected individuals may be protected against subsequent HIV-1 infection, the majority suggest no protection or even an increased risk of acquiring HIV-1 superinfection. We therefore propose to compare HIV-1 cross-neutralizing antibody responses and enhancing antibody responses in HIV-2 patients who go on to acquire HIV-1 superinfection, with those who have remained HIV-2 mono-infected despite possible exposure to HIV-1.||Such information could provide vital clues to how the HIV surface interacts with antibodies and the importance of eliciting an antibody response in future HIV vaccines.

Technical Summary

Twenty-five years after the beginning of the AIDS pandemic, gaps in knowledge limit the development of an effective vaccine. Understanding the molecular basis of a broad and potent neutralizing antibody (NAb) response in natural HIV infection is a gap that if filled could provide critical information relevant to HIV vaccine design. Exploring a potential role for protective humoral immunity in the majority of HIV-2 infected individuals who behave as long term non-progressors warrants further study, as does the possibility that in some HIV-2 infected individuals NAb responses may be cross-reactive and protect against subsequent HIV-1 infection. In contrast to HIV-1, potent NAb responses in HIV-2 were described in early reports and recent confirmatory findings using newer technology are very encouraging. Thus the primary objectives of this research are to:||1) Compare autologous NAb responses in HIV-1 and HIV-2 infected individuals with asymptomatic HIV infection and preserved CD4 counts; with HIV-2 infected individuals stratified into those who progress to advanced immunosuppression and those who remain long term non-progressors.||2) Compare HIV-1 cross-neutralizing and enhancing antibody responses in HIV-2 infected patients who subsequently go on to acquire HIV-1 coinfection, with those who remain HIV-2 mono-infected, matched as best possible for HIV-1 exposure.

Publications

10 25 50
 
Description Variation in tetherin antagonism by primary HIV-2 envelope isolates 
Organisation King's College London
Department School of Medicine KCL
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of HIV-2 envelope clones, obtained from a rural community cohort in Guinea-Bissau, from HIV-2 elite controllers, viraemic controllers and progressors.
Impact Work ongoing
Start Year 2009