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Pseudovirion particle production by live poxvirus human immunodeficiency virus vaccine vector enhances humoral and cellular immune responses.
- Source :
-
Journal of virology [J Virol] 2005 May; Vol. 79 (9), pp. 5537-47. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Animals
Antibody Specificity
CD4-Positive T-Lymphocytes immunology
Canarypox virus ultrastructure
Cytokines biosynthesis
Female
Gene Products, env genetics
Gene Products, env immunology
Genes, gag genetics
Genes, gag immunology
HIV Antibodies blood
HIV Infections blood
Interferon-gamma analysis
Interferon-gamma biosynthesis
Mice
Mice, Inbred BALB C
Vaccines, Synthetic immunology
AIDS Vaccines immunology
Canarypox virus genetics
Genetic Vectors genetics
Genetic Vectors ultrastructure
HIV Infections immunology
HIV-1 genetics
Immunization
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 79
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 15827168
- Full Text :
- https://doi.org/10.1128/JVI.79.9.5537-5547.2005