Study of the anti-HIV B cell response during acute infection

The initial antibody response to HIV-1 is non-neutralizing, targeted to gp41 envelope, and is ineffective in controlling viremia. To understand origins of gp41 antibody responses, we studied clonal lineages of gp41 antibodies isolated 17-30 days after transmission using single-cell antibody and reverted umutated antibody ancestor production. We found the reverted unmutated gp41 antibody ancestors frequently did not react with HIV-1 gp41 envelope, but instead were polyreactive and bound to host and bacterial antigens. In contrast, reverted unmutated ancestors of clonal lineages of influenza A hemagglutinin-specific B cells were not polyreactive and reacted with hemagglutinin. These data demonstrate that HIV-1 frequently diverts the initial envelope antibody response by stimulating mutated B cell clones originally activated by antigens other than HIV-1 envelope, thereby diverting initial antibody responses to be non-protective.