Pseudovirion particle production by live poxvirus human immunodeficiency virus vaccine vector enhances humoral and cellular immune responses.
Live-vector-based human immunodeficiency virus (HIV) vaccines are an integral part of a number of HIV vaccine regimens currently under evaluation. Live vectors that carry an intact gag gene are capable of eliciting HIV pseudovirion particle formation from infected host cells. The impact of pseudovirion particle formation on the immune response generated by live HIV vaccine vectors has not been established. In this study, a canarypox HIV vaccine candidate vector expressing HIV gag and env genes, vCP205, was modified by the introduction of a glycine-to-alanine coding change in the N-terminal myristylation site of gag to create Myr- vCP205. This substitution effectively eliminated particle formation without altering the level of protein production. vCP205 and Myr- vCP205 were then directly compared for the ability to induce HIV-specific immune responses in mice. The particle-competent vector vCP205 elicited higher levels of CD8+ T-cell responses, as indicated by gamma interferon enzyme-linked immunospot (ELISPOT) assay and intracellular cytokine staining. Humoral responses to Gag and Env were also markedly higher from animals immunized with the particle-competent vector. Furthermore, HIV-specific CD4+ T-cell responses were greater among animals immunized with the particle-competent vector. Using a human dendritic cell model of antigen presentation in vitro, vCP205 generated greater ELISPOT responses than Myr- vCP205. These results demonstrate that pseudovirion particle production by live-vector HIV vaccines enhances HIV-specific cellular and humoral immune responses.
Chen
Xuemin
X
Vanderbilt University School of Medicine, Pediatric Infectious Diseases, D-7235 MCN, Nashville, TN 37232-2581, USA.
Rock
Michael T
MT
Hammonds
Jason
J
Tartaglia
James
J
Shintani
Ayumi
A
Currier
Jeff
J
Slike
Bonnie
B
Crowe
James E
JE
Marovich
Mary
M
Spearman
Paul
P
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D028121:Canarypox virus / Q000235:genetics* / Q000648:ultrastructure; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015750:Genes, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics* / Q000648:ultrastructure; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics*; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D007371:Interferon-gamma