Generation of CD8+ T-cell responses by a recombinant nonpathogenic Mycobacterium smegmatis vaccine vector expressing human immunodeficiency virus type 1 env

Mark J. Cayabyab, Avi Hai Hovav, Tsungda Hsu, Georgia R. Krivulka, Michelle A. Lifton, Darci A. Gorgone, Glenn J. Fennelly, Barton F. Haynes, William R. Jacobs, Norman L. Letvin

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Because the vaccine vectors currently being evaluated in human populations all have significant limitations in their immunogenicity, novel vaccine strategies are needed for the elicitation of cell-mediated immunity. The nonpathogenic, rapidly growing mycobacterium Mycobacterium smegmatis was engineered as a vector expressing full-length human immunodeficiency virus type 1 (HIV-1) HXBc2 envelope protein. Immunization of mice with recombinant M. smegmatis led to the expansion of major histocompatibility complex class I-restricted HIV-1 epitope-specific CD8+ T cells that were cytolytic and secreted gamma interferon. Effector and memory T lymphocytes were elicited, and repeated immunization generated a stable central memory pool of virus-specific cells. Importantly, preexisting immunity to Mycobacterium bovis BCG had only a marginal effect on the immunogenicity of recombinant M. smegmatis. This mycobacterium may therefore be a useful vaccine vector.

Original languageEnglish (US)
Pages (from-to)1645-1652
Number of pages8
JournalJournal of virology
Volume80
Issue number4
DOIs
StatePublished - Feb 2006
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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