TY - JOUR
T1 - Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine
T2 - A randomized, double-blinded, controlled, multicenter trial
AU - Gorse, Geoffrey J.
AU - Keitel, Wendy
AU - Keyserling, Harry
AU - Taylor, David N.
AU - Lock, Michael
AU - Alves, Katia
AU - Kenner, Julie
AU - Deans, Lynne
AU - Gurwith, Marc
N1 - Funding Information:
Contributors: All authors contributed significantly to the writing and review of various portions of this article, and have approved for publication the final version and its contents. Geoffrey J. Gorse, Wendy Keitel, Harry Keyserling and David N. Taylor also were responsible for the conduct of the clinical study at their respective sites. Lynne Deans, Julie Kenner, and Marc Gurwith participated in the design, conduct, and monitoring of the rPA102 clinical study. Katia Alves, Julie Kenner, and Marc Gurwith reviewed and analyzed the clinical data; and Michael Lock was responsible for the statistical analysis of the data. Marc Gurwith was responsible for the overall supervision of the rPA102 study. Conflict of interest statement: Katia Alves, Lynne Deans, Marc Gurwith and Michael Lock are current employees of VaxGen Inc. and own either shares or stock options in the company. Julie Kenner was employed by VaxGen Inc. until June of 2005, and has remained as an independent consultant to the company. Harry Keyserling supports the development and testing of several potential anthrax vaccine candidates that can be regarded as competitors to rPA102. Geoffrey J. Gorse, Wendy Keitel and David N. Taylor do not have declared conflicts of interest. Funding: The study was funded by the National Institute of Allergy and Infectious Disease (NIAID) award N01-AI-25494.
PY - 2006/8/14
Y1 - 2006/8/14
N2 - Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p < 0.001) and the second (84.2% versus 35.4%; p < 0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.
AB - Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p < 0.001) and the second (84.2% versus 35.4%; p < 0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.
KW - Anthrax vaccines
KW - Clinical trial phase I
KW - Immunogenicity
KW - Recombinant vaccines
KW - Safety
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U2 - 10.1016/j.vaccine.2006.05.044
DO - 10.1016/j.vaccine.2006.05.044
M3 - Article
C2 - 16797805
AN - SCOPUS:33746058634
SN - 0264-410X
VL - 24
SP - 5950
EP - 5959
JO - Vaccine
JF - Vaccine
IS - 33-34
ER -