Induction of broad HIV-1 neutralizing antibodies should be a major goal of an effective HIV-1 vaccine. However, B cells are severely damaged during HIV-1 infection with loss of memory B cells and decline of serological memory. The molecular events leading to B cell damage must be further characterized with the aim of selecting vaccine components allowing preservation of B cell functions. This review focuses on B cell damage and antibody responses in HIV-1-infected patients during vaccination studies with viral and bacterial antigens. In addition novel data indicate that B cell activation may be at the basis of impaired immune responses.