Generation of CD8+ T-cell responses by a recombinant nonpathogenic Mycobacterium smegmatis vaccine vector expressing human immunodeficiency virus type 1 Env.
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.
Cayabyab
Mark J
MJ
Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02130, USA.
Hovav
Avi-Hai
AH
Hsu
Tsungda
T
Krivulka
Georgia R
GR
Lifton
Michelle A
MA
Gorgone
Darci A
DA
Fennelly
Glenn J
GJ
Haynes
Barton F
BF
Jacobs
William R
WR
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis; D020102:Mycobacterium smegmatis / Q000235:genetics* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D001428:Bacterial Vaccines; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic; D007371:Interferon-gamma