Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1.

Journal article

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.

Authors: Borthwick, N; Ahmed, T; Ondondo, B; Hayes, P; Rose, A

• Publication status: Published
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy
• Volume: 22
• Issue: 2
• Pages: 464-475
• Publication date: 2014-02-01
• DOI: 10.1038/mt.2013.248
• EISSN: 1525-0024
• ISSN: 1525-0016
• Language: English
• Keywords: pol Gene Products, Human Immunodeficiency Virus; T-Lymphocyte Subsets; Adult; HIV-1; Cells, Cultured; T-Cell Antigen Receptor Specificity; T-Lymphocytes; AIDS Vaccines; Vaccines, DNA; HIV Infections; Female; Adolescent; Amino Acid Sequence; Middle Aged; Molecular Sequence Data; Epitope Mapping; gag Gene Products, Human Immunodeficiency Virus; Epitopes, T-Lymphocyte; Male; Conserved Sequence; Young Adult; Humans; Virus Replication