Moving to Human Immunodeficiency Virus Type 1 Vaccine Efficacy Trials: Defining T Cell Responses As Potential Correlates of Immunity

Abstract

There is evidence in both simian immunodeficiency virus and human immunodeficiency virus (HIV) type 1 infection that class I major histocompatibility complex–restricted CD8⁺ cytotoxic T lymphocytes play a pivotal role in controlling infection and, potentially, in protecting by immunization. Progress has been made in designing strategies to elicit these responses with HIV-1 vaccines, but methods to reproducibly quantify them have posed difficulties. An interferon-γ enzyme-linked immunospot assay, using peptide pools spanning the HIV-1 genes, was developed and standardized. This method is rapid (2 days), sensitive (threshold of detection, ⩾0.005%), quantitative, feasible using cryopreserved cells, and able to define epitope specificities. When this assay was applied to 36 HIV-1–seropositive and 10 HIV-1–seronegative subjects, it proved to be robust (specificity, 100%). When responses in natural infection were compared with vaccine-induced responses, vaccine recipient responses were ⩾1 log lower, which confirms the importance of using this sensitive assay as an initial screen in vaccine protocols