title: Immediate-type hypersensitivity and other clinical reactions in volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAP1NYU) against Plasmodium falciparum sporozoites.
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.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Room 480, 685 West Baltimore Street, Baltimore, MD 21201 USA. redelman@medicine.umaryland.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Edelman
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: James G
authors.initials: JG
authors.lastname: Kublin
authors.forename: Sacared A
authors.initials: SA
authors.lastname: Bodison
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Nardin
authors.forename: Giane A
authors.initials: GA
authors.lastname: Oliveira
authors.forename: Sobia
authors.initials: S
authors.lastname: Ansari
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Kashala
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Schmeckpeper
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006805:Human Experimentation; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007428:Intradermal Tests; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D014581:Urticaria / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E