TY - JOUR
T1 - Immediate-type hypersensitivity and other clinical reactions in volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAP1NYU) against Plasmodium falciparum sporozoites
AU - Edelman, Robert
AU - Wasserman, Steven S.
AU - Kublin, James G.
AU - Bodison, Sacared A.
AU - Nardin, Elizabeth H.
AU - Oliveira, Giane A.
AU - Ansari, Sobia
AU - Diggs, Carter L.
AU - Kashala, Oscar L.
AU - Schmeckpeper, Barbara J.
AU - Hamilton, Robert G.
N1 - Funding Information:
We gratefully acknowledge the skilled clinical assistance of Helen Secrest, R.N. and Jo Anna Becker, R.N., and the technical assistance of Rita Altzsuler. We thank Drs. Oscar Kashala, Charlotte Kensil, and Robert Kammer, Aquila Biopharmaceuticals Inc. for the gift of clinical lots of QS-21 and for unpublished clinical and laboratory results using QS-21 in vaccine trials. We thank Dr. C.T. Shin, Reheis Inc. for the clinical lot of aluminum hydroxide used for skin tests. The (T1B) 4 MAP vaccine was bottled at WRAIR under the supervision of Dr. Kenneth Eckels, who also helped us develop the skin test reagents. We acknowledge Eveline Tierney, NIAID, NIH, for assistance with regulatory affairs and Dr. Lorraine Soisson, US Agency for International Development, for help in program coordination. Additional thanks to Dr. B. Fenton Hall, NIAID, NIH, for helpful discussions during the course of the study. Finally, we thank the volunteers for their loyal participation. Grant support: research contract NO1-AI-45251 to the University of Maryland; the work at New York University was supported by the National Institute of Allergy and Infectious Diseases grant (R01-AI-25085).
PY - 2002/12/13
Y1 - 2002/12/13
N2 - 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.
AB - 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.
KW - Cutaneous immediate-type hypersensitivity
KW - Malaria vaccine
KW - Phase I vaccine trial
UR - http://www.scopus.com/inward/record.url?scp=0037073595&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037073595&partnerID=8YFLogxK
U2 - 10.1016/S0264-410X(02)00468-1
DO - 10.1016/S0264-410X(02)00468-1
M3 - Article
C2 - 12450702
AN - SCOPUS:0037073595
SN - 0264-410X
VL - 21
SP - 269
EP - 280
JO - Vaccine
JF - Vaccine
IS - 3-4
ER -