Essential Role for Virus-Neutralizing Antibodies in Sterilizing Immunity against Friend Retrovirus Infection

The current experiments use the Friend retrovirus model to demonstrate that vaccine-primed B cells are essential for sterilizing immunity, and the results indicate that the requisite function of these cells is the production of virus-neutralizing antibodies rather than priming or reactivation of T cells. B cell-deficient mice were poorly protected by vaccination, but adoptive transfer experiments showed that the T cells from B cell-deficient mice were primed as well as those from wild-type mice. Furthermore, passive transfer of virus-neutralizing antibodies completely compensated for B cell deficiency. The presence of virus-neutralizing antibodies at the time of infection was crucial for vaccine efficacy. Interestingly, virus-neutralizing antibodies worked synergistically with vaccine-primed T cells to provide a level of protection many orders of magnitude greater than either antibodies or immune T cells alone. Nonneutralizing antibodies also contributed to protection and acted cooperatively with neutralizing antibodies to reduce infection levels. These results emphasize the importance of inducing both T cell responses and virus-neutralizing antibody responses for effective retroviral vaccine protection.