Extracting and Characterizing HIV-Neutralizing Antibodies from the Female Genital Tract of Vaccine Trial Patients South African
Authors:Melis Anahtar, Siduo Jiang
Mentor:Douglas Kwon, Instructor in Medicine and Infectious Diseases Specialist, Ragon Institute of MGH, MIT and Harvard
The HIV pandemic continues to burden more than 30 million individuals worldwide despite over 30 years research. Globally, over 90% of HIV transmission occurs during heterosexual intercourse, and most new cases arise in women between ages 14-25. As a result, the mucosal surface of the female genital tract (FGT) acts as a key target for vaccine design as it is the primary site of HIV acquisition in females. The CAPRISA 004 trial, conducted at Center for the AIDS Programme of Research at the University of Kwa-Zulu Natal in South Africa, tested the efficacy of a vaginal gel microbicide containing 1% tenofovir, an HIV reverse transcriptase inhibitor. It was found that the gel resulted in a 39% reduction in new HIV infection. However, the mechanism of this control is not yet understood, particularly the interaction between tenofovir and the local FGT immune system. It has been hypothesized that in addition to the protective drug, varied antibody responses may have played a role in protecting study patients who ultimately remained HIV uninfected. In order to better understand the mechanism of action, cytobrush samples from the cervix were collected from the trial patients in South Africa and analyzed using a cutting-edge single-cell analysis technology developed at MIT. From these samples, we have collected multidimensional immunological data. This technology incorporates a process known as microengraving which enables the identification of antibody-secreting cells, and the recovery of these cells for sequence retrieval. We have isolated several antibodies applying this method. These antibodies are mapped for HIV epitope specificity and sequenced for BCR analysis. A better understanding of the antibody response in these women could provide clues to better improve future microbicides and develop more efficacious vaccines to prevent HIV acquisition in women.