Inclusion of the viral anti-apoptotic molecule M11L in DNA vaccine vectors enhances HIV Env-specific T cell-mediated immunity.
A current goal of vaccine development against human immunodeficiency virus (HIV) is to develop a strategy that stimulates long-lasting memory T-cell responses, and provides immediate cytotoxicity in response to viral challenge. We demonstrate that the viral antiapoptotic molecule M11L promotes cellular immune responses to the HIV envelope protein. Coexpression of M11L in vitro inhibits gp140-mediated apoptosis and increases gp140 expression levels. Mice primed with M11L-pHERO DNA, followed by vCP205 boosting, exhibit significantly greater HIV-specific T-cell responses. Moreover, M11L synergizes with CpG motifs to augment anti-HIV responses and stimulates robust expansion of central memory and effector memory CD8(+) T-cells. Inclusion of M11L in a DNA vector increases the magnitude of T-cell responses, and promotes the generation of memory T-cells that provide rapid-responding CTL responses. This vaccine strategy may facilitate the generation of an efficacious vaccine for HIV, and other chronic diseases that require enhanced cell-mediated immunity, including HCV and metastatic cancer.
Su
Jin
J
Biotherapeutics Research Group, Robarts Research Institute, Canada; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada, N6A 5K8.
Willert
Christy
C
Comanita
Lacrimioara
L
Peters
Andrew
A
Gilbert
Philippe-Alexandre
PA
Strathdee
Craig
C
O'Connell
Peta J
PJ
McFadden
Grant D
GD
Dekaban
Gregory A
GA
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C077309:M11L protein, Myxoma virus