title: Phase 1 study of a recombinant mutant protective antigen of Bacillus anthracis.
abstract: A phase 1 study of a recombinant mutant protective antigen (rPA) vaccine was conducted in 186 healthy adults aged 18 to 45 years. Volunteers were randomized to receive one of three formulations of rPA (formalin treated, alum adsorbed, or both), in 10- or 20-μg dosages each, or the licensed vaccine, AVA. Three injections were given at 2-month intervals and a 4th 1 year after the 3rd. Vaccinees were examined at the clinic once following each injection, at 48 to 72 h postinjection. Adverse reactions were recorded in diaries for 7 days. Sera were collected before each injection and 1 week after the 1st, 2 weeks after the 3rd and 4th, and 1 year after the 4th. Serum anti-PA IgG was assayed by enzyme-linked immunosorbent assay (ELISA) and toxin neutralization assay (TNA). All formulations at both dosages were safe and immunogenic, inducing booster responses, with the highest antibody levels following the 4th injection (354 to 732 μg/ml). The lowest levels were induced by the formalin-only-treated rPA; there was no statistical difference between levels induced by alum-adsorbed and formalin-treated/alum-adsorbed rPA or by the two dosages. The antibody levels declined in all groups during the 1-year intervals after the 3rd and 4th injections but less so during the 2nd year, after the 4th injection (fold decreases were 10 to 25 versus 3.4 to 7.0, P < 0.001). There were too few AVA recipients for statistical comparisons, but their antibody levels followed those of rPA. Anti-rPA measured by ELISA correlated with TNA titers (r = 0.97). These data support studying alum-adsorbed rPA in children.
authors.affiliation: Program in Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Bellanti
authors.forename: Feng-Ying C
authors.initials: FY
authors.lastname: Lin
authors.forename: Chiayung
authors.initials: C
authors.lastname: Chu
authors.forename: Joseph
authors.initials: J
authors.lastname: Shiloach
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
authors.forename: German A
authors.initials: GA
authors.lastname: Benavides
authors.forename: Arthur
authors.initials: A
authors.lastname: Karpas
authors.forename: Mahtab
authors.initials: M
authors.lastname: Moayeri
authors.forename: Chunyan
authors.initials: C
authors.lastname: Guo
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C030325:anthrax toxin