Viral Inhibition Assay: A CD8 T Cell Neutralization Assay for Use in Clinical Trials of HIV-1 Vaccine Candidates

• Published in: The Journal of infectious diseases Vol. 201; no. 5; pp. 720 - 729
• Main Authors: Spentzou, Aggeliki, Bergin, Philip, Gill, Dilbinder, Cheeseman, Hannah, Ashraf, Ambreen, Kaltsidis, Harry, Cashin-Cox, Michelle, Anjarwalla, Insiyah, Steel, Alan, Higgs, Christopher, Pozniak, Anton, Piechocka-Trocha, Alicja, Wong, Johnson, Anzala, Omu, Karita, Etienne, Dally, Len, Gotch, Frances, Walker, Bruce, Gilmour, Jill, Hayes, Peter
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 01.03.2010; University of Chicago Press; Oxford University Press
• Subjects: Adenovirus; Adenoviruses, Human - genetics; Adult; Aged; AIDS Vaccines - genetics; AIDS Vaccines - immunology; Applied microbiology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Clinical trials; Cultured cells; Enzyme linked immunospot assay; Enzyme-Linked Immunosorbent Assay - methods; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors; HIV; HIV 1; HIV-1 - immunology; HIV/AIDS; Human immunodeficiency virus 1; Humans; Infections; Infectious diseases; Lymphocytes; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Neutralization Tests - methods; Placebos; Reproducibility of Results; Sensitivity and Specificity; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; Virus Replication - immunology; Viruses; Virus; Infection; HIV-1 virus; T-Lymphocyte; Retroviridae; Clinical trial; Vaccine; Human immunodeficiency virus; Lentivirus; Neutralization
• ISSN: 0022-1899; 1573-6613; 1537-6613
• DOI: 10.1086/650492

We have characterized an assay measuring CD8 T cell-mediated inhibition of human immunodeficiency virus (HIV) type 1 replication, demonstrating specificity and reproducibility and employing a panel of primary HIV-1 isolates. The assay uses relatively simple autologous cell culture and enzyme-linked immunosorbent assay, avoids generation of T cell clones, and can be performed with <2 million peripheral blood mononuclear cells. Efficient CD8 T cell-mediated cross-clade inhibition of HIV-1 replication in vitro was demonstrated in antiretroviral therapy-naive HIV-1-infected subjects with controlled viral replication in vivo but not in viremic subjects. An HIV-1 vaccine candidate, consisting of DNA and recombinant adenovirus 5 vectors tested in a phase I clinical trial, induced CD8 T cells that efficiently inhibited HIV-1 in a HLA-I-dependent manner. Assessment of direct antiviral T cell function by this assay provides additional information to guide vaccine design and the prioritizing of candidates for further clinical trials.