Antagonism of vaccine-induced HIV-1-specific CD4+ T cells by primary HIV-1 infection: potential mechanism of vaccine failure
Kent, S.J.; Greenberg, P.D.; Hoffman, M.C.; Akridge, R.E.; McElrath, M.J.
Journal of Immunology 158(2): 807-815
1997
ISSN/ISBN: 0022-1767 PMID: 8992998 Document Number: 473166
Prior immunity to HIV-1 elicited by vaccination may modify subsequent responses upon exposure to infectious HIV-1. An HIV-1-uninfected person entered in a vaccine trial that included immunization to HIV-1LAI envelope with a recombinant vaccinia vector and recombinant protein developed envelope-specific CD4+ T cell responses, including proliferative and cytolytic responses, but was not protected from a high risk HIV-1 exposure. CD4+ T cell clones derived from blood at the peak of vaccine-induced immunity recognized and lysed autologous target cells expressing 4 distinct regions within the HIV-1LAI envelope region; 3 of these CTL clones also recognized targets expressing envelope from a similar viral subtype, HIV-1MN. The epitope specificity of CD4+ clone 9G8, recognizing both HIV-1LAI and HIV-1MN envelope, was within the 571-590 amino acid envelope region. Sequence analysis of the first infectious autologous strain revealed 2 amino acid mutations within this region. The 9G8 CTL clone induced by immunization failed to recognize targets expressing the corresponding CTL epitope from the infecting virus. Moreover, a peptide based on the epitope sequence of the infecting isolate antagonized the vaccine-induced CTL clone such that the CTL clone was no longer able to recognize the vaccine strain or HIV-1MN epitope. A potentially novel mechanism associated with vaccine failure whereby the infecting virus may not only escape from CTL activity, but also alter the ability of CTL to recognize other variants in an individual is suggested.