Back to Search
Start Over
Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice.
- Source :
- PLoS ONE; 3/9/2017, Vol. 12 Issue 3, p1-13, 13p
- Publication Year :
- 2017
-
Abstract
- In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-Gag<superscript>M</superscript>, MVA-Gag<superscript>M</superscript> and DNA-Gag<superscript>M</superscript>). Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that Gag<superscript>M</superscript> buds from cells infected and transfected with MVA-Gag<superscript>M</superscript> and DNA-Gag<superscript>M</superscript> respectively and forms virus-like particles. Previously we showed that a BCG-Gag<superscript>M</superscript> prime MVA-Gag<superscript>M</superscript> boost generated strong cellular immune responses in mice. In this study immune responses to the DNA-Gag<superscript>M</superscript> and MVA-Gag<superscript>M</superscript> vaccines were evaluated in homologous and heterologous prime-boost vaccinations. The DNA homologous prime boost vaccination elicited predominantly CD8+ T cells while the homologous MVA vaccination induced predominantly CD4+ T cells. A heterologous DNA-Gag<superscript>M</superscript> prime MVA-Gag<superscript>M</superscript> boost induced strong, more balanced Gag CD8+ and CD4+ T cell responses and that were predominantly of an effector memory phenotype. The immunogenicity of the mosaic Gag (Gag<superscript>M</superscript>) was compared to a naturally occurring subtype C Gag (Gag<superscript>N</superscript>) using a DNA homologous vaccination regimen. DNA-Gag<superscript>N</superscript> expresses a natural Gag with a sequence that was closest to the consensus sequence of subtype C viruses sampled in South Africa. DNA-Gag<superscript>M</superscript> homologous vaccination induced cumulative HIV-1 Gag-specific IFN-γ ELISPOT responses that were 6.5-fold higher than those induced by the DNA-Gag<superscript>N</superscript> vaccination. Similarly, DNA-Gag<superscript>M</superscript> vaccination generated 7-fold higher levels of cytokine-positive CD8+ T cells than DNA-Gag<superscript>N</superscript>, indicating that this subtype C mosaic Gag elicits far more potent immune responses than a consensus-type Gag. Cells transfected and infected with DNA-Gag<superscript>M</superscript> and MVA-Gag<superscript>M</superscript> respectively, expressed high levels of Gag<superscript>M</superscript> and produced budding virus-like particles. Our data indicates that a heterologous prime boost regimen using DNA and MVA vaccines expressing HIV-1 subtype C mosaic Gag is highly immunogenic in mice and warrants further investigation in non-human primates. [ABSTRACT FROM AUTHOR]
- Subjects :
- DNA vaccines
HIV
GENE expression
MOSAIC viruses
LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 121694135
- Full Text :
- https://doi.org/10.1371/journal.pone.0173352