ANTAGONISM OF VACCINE-INDUCED HIV-1-SPECIFIC CD4(-CELLS BY PRIMARY HIV-1 INFECTION - POTENTIAL MECHANISM OF VACCINE FAILURE() T)

Prior immunity to HIV-I elicited by vaccination may modify subsequent responses upon exposure to infectious HIV-1. An HIV-1-uninfected perso n entered in a vaccine trial that included immunizations to HIV-1(LAI) envelope with a recombinant vaccinia vector and recombinant protein d eveloped envelope-specific CD4(+) T cell responses, including prolifer ative and cytolytic responses, but was not protected from a high risk HIV-1 exposure. CD4(+) T cell clones derived from brood at the peak of vaccine-induced immunity recognized and lysed autologous target cells expressing four distinct regions within the HIV-1(LAI) envelope regio n; three of these CTL clones also recognized targets expressing envelo pe from a similar viral subtype, HIV-(MN). The epitope specificity of CD4(+) clone 9G8, recognizing both HIV-1(LAI) and HIV-1(MN) envelope, was within the 571-590 amino acid envelope region. Sequence analysis o f the first infectious autologous strain revealed two amino acid mutat ions within this region. The 9G8 CTL clone induced by immunization fai led to recognize targets expressing the corresponding CTL epitope from the infecting virus. Moreover, a peptide based on the epitope sequenc e of the infecting isolate antagonized the vaccine-induced CTL clone s uch that the CTL clone was no longer able to recognize the vaccine str ain or HIV-1(MN) epitope. These findings suggest a potentially novel m echanism associated with vaccine failure whereby the infecting virus m ay not only escape from CTL activity, but also alter the ability of CT L to recognize other variants in an individual.