They found that the plasma more potently neutralized the HIV variants compared to the individual nAbs, suggesting that neutralization activity might be mediated by antibodies that were not isolated in the screen. The investigators then tested the neutralization capacity of both the maternal plasma, which contains a mixture of all antibodies, and individual representatives of the 21 nAb families against several “Tier 1” and “Tier 2” HIV-1 viruses. The authors selected an easy-to-neutralize “Tier 1A” HIV-1 variant in an attempt to cast a wide net to study the highest number of maternal antibodies from this subject. Through this methodology, the group was able to isolate and confirm the neutralizing activity of 39 monoclonal antibodies, which originated from 21 clonal B-cell families.

Using a high-throughput functional screen, the investigators cultured and screened individual B-cells for the production of antibodies with the capacity to neutralize an HIV-1 variant. The investigators first isolated memory B-cells –immune cells that produce antibodies– from the sample collected from the mother at 31-weeks of pregnancy. The baby was born prematurely at 32-weeks of gestation, but the virus was not detected in the newborn until six weeks of age. The mother had been HIV-positive at the time of enrollment in the study, and a blood sample was collected at 31 weeks of pregnancy. To test this hypothesis, the investigators selected a mother-child sample pair to characterize the repertoire of maternal nAbs. The authors hypothesized that selection for transmission of a particular maternal HIV variant, and not others, could be partially mediated by maternal nAbs. It is well-documented that infants who get infected in an MTCT setting only acquire a few of the maternal HIV variants. The group recently published their findings in the Journal of Virology. The Overbaugh lab (Human Biology) sought to better understand how the mother’s antibody response affects the viruses that are transmitted to infants using samples obtained 20 years ago in a longitudinal HIV study from Kenya, before effective antiretroviral therapies were developed. Therefore, characteristics of maternal HIV-specific antibodies that protect infants against infection could inform HIV vaccine design. In the absence of antiviral therapy for the mother or infant, HIV-infected mothers can transmit HIV to their babies during pregnancy, delivery, or through breastfeeding however, only 30-40% of infants in this setting become infected. Such nAbs are likely to protect against mother-to-child transmission (MTCT) of HIV. HIV-specific neutralizing antibodies (nAbs) bind to the HIV envelope (Env), a protein on the surface of the viral particle that binds CD4 receptors on T-cells and mediates entry into the cell. An effective HIV vaccine would have to stimulate the immune system to produce antibodies that can bind to the virus and prevent infection of target cells –an event known as neutralization. The development of a vaccine against HIV has been a global health priority since the mid-1980s, but, to this day, a successful vaccine remains elusive. Viruses, Vaccines and Infectious Diseases.Institutional Partners & Collaborations.

Vaccine and Infectious Disease Division.

Antibody repertoire gestation