Generation of mucosal anti-human immunodeficiency virus type 1 T-cell responses by recombinant Mycobacterium smegmatis.
A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 immune responses at mucosal sites. We have generated recombinant Mycobacterium smegmatis vectors that express the HIV-1 group M consensus envelope protein (Env) as a surface, intracellular, or secreted protein and have tested them in animals for induction of both anti-HIV-1 T-cell and antibody responses. Recombinant M. smegmatis engineered for expression of secreted protein induced optimal T-cell gamma interferon enzyme-linked immunospot assay responses to HIV-1 envelope in the spleen, female reproductive tract, and lungs. Unlike with the induction of T-cell responses, priming and boosting with recombinant M. smegmatis did not induce anti-HIV-1 envelope antibody responses, due primarily to insufficient protein expression of the insert. However, immunization with recombinant M. smegmatis expressing HIV-1 Env was able to prime for an HIV-1 Env protein boost for the induction of anti-HIV-1 antibody responses.
Yu
Jae-Sung
JS
Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Peacock
James W
JW
Vanleeuwen
Stacie
S
Hsu
Tsungda
T
Jacobs
William R
WR
Cayabyab
Mark J
MJ
Letvin
Norman L
NL
Frothingham
Richard
R
Staats
Herman F
HF
Liao
Hua-Xin
HX
Haynes
Barton F
BF
D000818:Animals; D003001:Cloning, Molecular; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D014170:Transformation, Genetic; D054299:env Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1