Phase I Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

• Published in: PloS one Vol. 5; no. 11; p. e13849
• Main Authors: Brown, Bruce K., Cox, Josephine, Gillis, Anita, VanCott, Thomas C., Marovich, Mary, Milazzo, Mark, Antonille, Tanya Santelli, Wieczorek, Lindsay, McKee, Kelly T., Metcalfe, Karen, Mallory, Raburn M., Birx, Deborah, Polonis, Victoria R., Robb, Merlin L.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.11.2010; Public Library of Science (PLoS)
• Subjects: Adjuvants; Adolescent; Adult; Adults; Age; Anthrax; Anthrax - immunology; Anthrax - prevention & control; Anthrax vaccines; Anthrax Vaccines - administration & dosage; Anthrax Vaccines - adverse effects; Anthrax Vaccines - genetics; Anthrax Vaccines - immunology; Antibodies; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacillus anthracis; Bacillus anthracis - genetics; Bacillus anthracis - immunology; Biological & chemical terrorism; Cell Proliferation - drug effects; Clinical outcomes; Clinical trials; Contamination; Dose-Response Relationship, Drug; Double-Blind Method; E coli; Enzyme-Linked Immunosorbent Assay; Enzymes; Erythema - chemically induced; Escherichia coli; Escherichia coli - genetics; Fatigue - chemically induced; Humans; Immune response (humoral); Immunization; Immunogenicity; Immunoglobulin G; Immunoglobulins; Immunology; Immunology/Immune Response; Infectious Diseases; Infectious Diseases/Bacterial Infections; Lymphocytes; Lymphocytes - cytology; Lymphocytes - drug effects; Lymphocytes - immunology; Pain - chemically induced; Protective antigen; Rabbits; Recombinant Proteins - immunology; Safety; Studies; Toxins; Vaccination - methods; Vaccines; Young Adult; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013849

The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA). A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. ClinicalTrials.gov NCT00057525.