"The Role of Neutralizing Antibodies in HIV-1 Transmission and Pathogenesis"
An important goal of HIV-1 vaccine design is to elicit neutralizing antibodies (NAbs) that would block viral entry to prevent infection, or effectively control viral replication if infection occurs. Despite over two decades of research, the role of NAbs in preventing or modulating the course of HIV-1 infection remains unclear. Most previous studies on the role of NAbs in disease progression used a panel of heterologous HIV-1 strains as a surrogate measure of NAb activity within a patient. However, these responses may not accurately reflect those against the autologous viruses that are actually present in the patient. Importantly, no study has investigated whether early autologous NAbs (aNAbs) capable of recognizing the infecting virus can provide clinical benefit. Using a well-established prospective cohort of HIV-1 infected women in Kenya, I will test the hypothesis that potent early aNAb responses control viral replication to delay disease progression. This finding would suggest that NAbs should be a component of a therapeutic vaccine. Additionally, in order for NAbs to be effective as a preventive vaccine, they must recognize diverse circulating strains. Recently, a number of monoclonal antibodies with broad HIV-1 neutralizing activity have been isolated from chronically infected patients, yet there is no data to suggest that these broadly neutralizing antibodies (bNAbs) will be effective against transmitted variants. Therefore, I will test the activity of these bNAbs against a panel of transmitted variants and investigate factors that might predict sensitivity to these bNAbs.