Delayed-type hypersensitivity in volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAP1NYU) against Plasmodium falciparum sporozoites

Abstract

During the testing of the safety and immunogenicity of an adjuvanted, synthetic Plasmodium falciparum CS multiple antigen peptide (MAP) vaccine, we investigated the potential for using cutaneous delayed-type hypersensitivity (DTH) reactions as a correlate of immune response. We evaluated 27 of our volunteers for DTH reactions to intradermal inoculation (0.02 ml) of several concentrations of the MAP vaccine and adjuvant control solutions. Induration was measured 2 days after skin tests were applied. Nine of 14 vaccinees (64%) with serum, high-titered anti-MAP antibody developed positive DTH (≥5 mm induration), that first appeared by 29 days after immunization and persisted for at least 3–6 months after 1–2 more immunizations. In contrast, DTH responses were negative in eight of eight vaccinees with no or low antibody titers, and in five of five non-immunized volunteers. Biopsies of positive DTH skin test sites were histologically compatible with a DTH reaction. We conclude that the presence of T cell functional activity reflected by a positive DTH skin test response to the MAP antigen serves as another marker for vaccine immunogenicity.