Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans

The phase 2b trial of Merck's recombinant adenovirus type 5–based HIV-1 vaccine was halted as the vaccine seemed to have increased HIV-1 acquisition in vaccine recipients who had preexisting immunity to the adenovirus vector. One theory to explain these results is that the preexisting antibody response to the vector may have been a surrogate for increased vector-specific CD4+ T cells, which would have been amplified after vaccination and may have served as increased target cells during subsequent HIV-1 exposure. Daniel Barouch and his colleagues and Michael Betts and his colleagues now challenge this view.