Researchers at The Scripps Research Institute (TSRI) discovered that an antibody that binds and neutralizes HIV likely also targets the body's own "self" proteins. This finding could complicate the development of HIV vaccines designed to elicit this protective antibody, called 4E10, and others like it, as doing so might be dangerous or inefficient.
"We developed two new mouse models that allow us to visualize the fate of the rare B cells that can see HIV and we thought could be stimulated by vaccines to produce neutralizing antibodies - the type of antibodies we seek to produce in response to a vaccine," said David Nemazee, PhD, professor in the Department of Immunology and Microbial Science at TSRI and senior author of the study. "We were able to study vaccine responses of b12, an antibody that sees the CD4 binding site of HIV, but, surprisingly to us, not 4E10, an antibody that sees the stem of the HIV envelope protein."
Nemazee and his team went on to discover that cells with the potential to produce 4E10 antibodies trigger several natural safeguards that shut down the production of any antibody that might recognize and destroy the body's own tissues. They concluded that 4E10 cross-reacts with host tissues in this way, prompting its removal before it can do any harm - or good. The study was recently published by The Journal of Immunology.
HIV Vaccine Development
4E10 antibodies were originally isolated from a human HIV patient. The antibodies specifically recognize and bind an HIV surface protein called gp41. The virus uses gp41 like a long spike to poke holes in its host's immune cells. But when 4E10 antibodies clog up gp41, the virus is neutralized and host cells are protected.
