Increased detection of proliferating, polyfunctional, HIV‐1‐specific T cells in DNA‐modified vaccinia virus Ankara‐vaccinated human volunteers by cultured IFN‐γ ELISPOT assay

AbstractInduction of a long‐term immunological memory, which can expand and defend the host upon pathogen encounter, is the “holy grail” of vaccinology. Here, using a sensitive cultured IFN‐γ ELISPOT assay, we show that 50% (15 out of 30) of healthy, HIV‐1/2‐uninfected volunteers who received pTHr.HIVA DNA prime‐modified vaccinia virus Ankara. HIVA boost vaccine regimen 1 to 3 1/2 years ago had detectable HIV‐1‐specific T‐cell responses. These T cells, predominantly of the CD4+ subtype, could proliferate and produce multiple cytokines in response to in vitro peptide stimulation. Peptide mapping studies showed that the vaccine‐induced CD4+ T cells were mostly directed toward epitopes targeted in HIV‐1‐infected individuals. In addition, we used the same assay to re‐evaluate 51 volunteers from past vaccine trial IAVI‐006 and corrected the previously reported 10% of vaccine responders to 50%. Thus, we confirmed that cultured assays are a valuable tool for studying T‐cell memory. These results are discussed in the context of the current state‐of‐affairs of the HIV‐1 vaccine field.