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Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4(+) cells and inhibited HIV-1 replication by up to 5.79 log10. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8(+) T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.

Original publication




Journal article


Mol Ther

Publication Date





464 - 475


AIDS Vaccines, Adolescent, Adult, Amino Acid Sequence, Cells, Cultured, Conserved Sequence, Epitope Mapping, Epitopes, T-Lymphocyte, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Molecular Sequence Data, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets, T-Lymphocytes, Vaccines, DNA, Virus Replication, Young Adult, gag Gene Products, Human Immunodeficiency Virus, pol Gene Products, Human Immunodeficiency Virus