Project Title

Evolution of neutralizing antibodies among acute to early HIV Subtype C infected individuals in Botswana: one year longitudinal study.

EDCTP Project Call

Senior Fellowship (SF)

Project Objectives

To characterise the evolution of neutralising antibodies against HIV-1 subtype C gp 120 molecular envelope clones from acute/and early heterosexual acquired HIV-1 subtype C infections in Botswana

Study Design

Prospective cohort study on the evolution of neutrolising antibodies in HIV –C

Project Summary

Over thirty years after the discovery of HIV, there is still no potent and efficacious vaccine against the infection. The recent discovery of potent and broad neutralizing antibodies against HIV-1 has revived the interest in the search for more of these antibodies and to investigate their possible role in preventing the infection. A cohort of eight HIV-1C acutely infected individuals were enrolled and followed for a period of up to 24 months. Plasma samples were collected at different time points during the follow-up and stored at -80ºC. Viral RNA was extracted from the plasma of these individuals collected at or around baseline as well as 6 months post enrolment and the envelope protein, glycoprotein 160, amplified. The HIV-1C envelope gene from these individuals was cloned into pcDNA3.1D/V5-His expression vector. The envelope clones were subsequently used to co-transfect 293 T cells along with a backbone vectors to produce pseudoviruses. A standardized neutralization assay based on TZM-bl cells was used to determine the autologous neutralizing capacity. All but one individual’s envelope pseudotyped viruses were neutralized by some of the autologous plasma albeit very late. Viruses generated during the acute infection period displayed varying neutralization sensitivities towards autologous plasma. Potency of the neutralization increased with time post infection time point. Neutralizing antibody development lags behind as evidenced by the lack of neutralizing capacity of the plasma to the contemporaneous HIV viral envelope generated from the primary infection. While the mutated viral species present at 6 months show a similar trend but there is fast development of neutralizing antibodies that become effective 3 months later. One of the individuals showed sharp decrease of the viral load at the same time there was marked increase in potent neutralizing antibodies. HIV-1 subtype C neutralizing antibodies from primary infection develops much later, around 5 months with significant potency increasing at around 2 years post infection. While any subsequent viral strains generated from mutation are rapidly recognized by the developing immune response, especially post introduction of antiretroviral treatment. This has given interesting pointers to HIV vaccine development and design for prevention working together with treatment.

Host Organisation

Sites

Results & Outcomes

Current Organisation

University of Zimbabwe

Current Job Title

Professor

Biography