title: An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals.
abstract: Samples of human plasma from anthrax vaccine adsorbed (AVA, BioThrax)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 microg of anti-PA IgG was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). Mice showed significant survival (p<or=0.001) after injection of serial dilutions up to 1:4 of the standard plasma and challenged with 100 LD50. Similarly, mice injected with the standard anti-AVA plasma and challenged up to 5 days post-treatment also survived (p<or=0.001). Using a cohort of human plasma to measure passive protection, the best correlation between passive protection and an in vitro assay was found to be with the quantitative toxin neutralization assay (minimum fold increase in odds of survival: 2.71, p=0.0062). These results demonstrate a reliable in vivo neutralization method that correlates with standard in vitro measures of neutralizing antibody levels in plasma from individuals vaccinated with the standard anthrax vaccine. This analytical method may provide additional opportunities to compare the efficacy of improved anthrax vaccines with the licensed vaccine.
authors.affiliation: United States Army Medical Research Institute of Infections Diseases (USAMRIID), Fort Detrick, MD 21702, United States. jhewetson@comcast.net
authors.forename: John F
authors.initials: JF
authors.lastname: Hewetson
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Little
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Ivins
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Johnson
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Pittman
authors.forename: J Edward
authors.initials: JE
authors.lastname: Brown
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Norris
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage* / Q000276:immunology*; D007116:Immunization, Passive; D051379:Mice; D009500:Neutralization Tests; D013223:Statistics as Topic; D016019:Survival Analysis
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007106:Immune Sera