Are the Targets of Broadly Neutralizing Antibodies on the Virus that Establishes Infection?
All of the recently identified broadly neutralizing antibodies against HIV have been isolated from chronically HIV-infected volunteers. In a presentation at AIDS Vaccine 2011, Penny Moore of the National Institute of Communicable Diseases in Johannesburg, South Africa, addressed the question of whether the epitopes that are the targets of these broadly neutralizing antibodies that develop later in the course of infection are present in the transmitted founder virus that establishes infection.
To evaluate this, Moore used samples collected from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 cohort of acutely infected individuals. Seven of the 40 volunteers from CAPRISA 002 that Moore and colleagues analyzed developed broadly cross-reactive neutralizing antibody responses. They also analyzed the transmitted founder viruses from additional volunteers who developed broadly neutralizing antibodies from the CAPRISA 004 cohort.
The antibodies that developed in these volunteers targeted different epitopes on the virus. Some targeted epitopes in the second variable (V2) loop of HIV Envelope, while others targeted glycans.
Moore and colleagues found that in five of the ten individuals analyzed, the epitope for the broadly neutralizing antibodies that developed later in infection were absent on the transmitted founder virus. However, the virus evolved to contain this epitope in some of the volunteers within six months of infection.
In one volunteer, Moore showed that the epitope target of the antibody was added to the virus as a direct result of a mutation to escape earlier antibody responses. "The way the virus develops has implications for the later broadly neutralizing antibody response," concluded Moore.