Design and pre-clinical evaluation of a universal HIV-1 vaccine.
Design and pre-clinical evaluation of a universal HIV-1 vaccine.
Blog Article
BACKGROUND:One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.METHODOLOGY AND FINDINGS:To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein.Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, 30hh bikini C and D, which alternate to ensure equal clade coverage.The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice.
We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection.SIGNIFICANCE:Therefore, this vaccine approach provides an attractive metabo 15-gauge finish nailer cordless and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape.Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.