ABSTRACT
We tested the clinical reactions to a synthetic, Plasmodium falciparum, circumsporozoite multiple antigen peptide (MAP) vaccine in 39 volunteers immunized two to three times over 2-8 months using a dose escalation design. Immediate pain at the injection site was associated with the adjuvant QS-21 (P<0.001), and delayed local inflammatory reactions were associated with high-titered circulating IgG anti-MAP antibody (P=0.03). Because two volunteers developed acute, systemic urticaria after the third immunization associated with development of serum IgE MAP antibody, we employed immediate-type hypersensitivity skin tests (ITH-STs) using intradermal injections of diluted MAP vaccine to identify persons sensitized to the vaccine. ITH-STs were negative in seven volunteers tested 27 days after the first vaccination, but six of these individuals developed positive wheal and flare reactions when tested 14 or 83 days after the second vaccination; IgE MAP antibody was detected in only one of them. Another cohort of 16 volunteers, including the 2 allergic individuals, were ITH-ST negative when first tested late after their second or third vaccination at 6-7 months. Five of five non-immunized persons were also ITH-ST negative. ITH-STs may help identify individuals sensitized to malaria peptides and at potential risk of developing systemic allergic reactions after re-vaccination.
Subject(s)
Antigens, Protozoan/immunology , Hypersensitivity, Delayed/chemically induced , Malaria Vaccines/adverse effects , Plasmodium falciparum/immunology , Adjuvants, Immunologic/administration & dosage , Adult , Animals , Antigens, Protozoan/biosynthesis , Cohort Studies , Female , Human Experimentation , Humans , Hypersensitivity/etiology , Immunoglobulin E/biosynthesis , Immunoglobulin G/biosynthesis , Intradermal Tests , Malaria Vaccines/administration & dosage , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Male , Pain/chemically induced , Pain/immunology , Plasmodium falciparum/growth & development , Urticaria/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Vaccines, Synthetic/pharmacologyABSTRACT
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 (>or=5mm 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.
