Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis.
The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4+ T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant-mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant-mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8+ T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.
Hovav
Avi-Hai
AH
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA.
Cayabyab
Mark J
MJ
Panas
Michael W
MW
Santra
Sampa
S
Greenland
John
J
Geiben
Ralf
R
Haynes
Barton F
BF
Jacobs
William R
WR
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D054301:gag Gene Products, Human Immunodeficiency Virus; C061169:p18 gag protein, Human immunodeficiency virus 1