Very few cases have been documented in which vaccine-elicited antibodies can bind to the Man1(alpha)-2Man1(alpha)-2Man ?tips? of Man8/9 high-mannose glycans that are prevalent on the HIV envelope protein. Rather, there is evidence that in most cases, vaccination with Man8/9 structures elicits antibodies that bind to the ?core? of the glycan, and pharmacokinetic literature data show that Man9 structures are rapidly trimmed to Man5/6 structures in vivo, on a timescale that may interfere with development of antibodies specific for Man9. The goal of this project is to test whether sustained immunogen delivery methods can increase the elicitation of antibodies specific for the intact Man8/9 glycans, by making intact glycan continuously available to the immune system.
Some HIV-infected individuals produce antibodies that neutralize many different strains of HIV, despite the virus' ability to mutate. Very often, these antibodies bind to a carbohydrate structure on the viral surface, but there has been difficulty developing vaccines that will stimulate the production of similar carbohydrate-binding antibodies. A possible reason for this difficulty is that the carbohydrate in the vaccine is degraded too quickly after injection; the proposed research will test whether a slow- release immunization regimen that continuously supplies the intact carbohydrate structure can better stimulate better production of the desired antibodies.
