title: Evaluation of early immune response-survival relationship in cynomolgus macaques after Anthrax Vaccine Adsorbed vaccination and Bacillus anthracis spore challenge.
abstract: Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved by the US Food and Drug Administration for post-exposure prophylaxis (PEP) of anthrax in adults. The PEP schedule is 3 subcutaneous (SC) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. The objectives of this study were to understand the onset of protection from AVA PEP vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf). We determined the efficacy against inhalation anthrax in nonhuman primates (NHP) of the first two doses of the PEP schedule by infectious challenge at the time scheduled for receipt of the third PEP dose (Day 28). Forty-eight cynomolgus macaques were randomized to five groups and vaccinated with serial dilutions of AVA on Days 0 and 14. NHP were exposed to Bacillus anthracis Ames spores on Day 28 (target dose 200 LD50equivalents). Anti-protective antigen (PA) IgG and toxin neutralizing antibody (TNA) responses to vaccination and in post-challenge survivors were determined. Post-challenge blood and selected tissue samples were assessed for B. anthracis at necropsy or end of study (Day 56). Pre-challenge humoral immune responses correlated with survival, which ranged from 24 to 100% survival depending on vaccination group. Surviving, vaccinated animals had elevated anti-PA IgG and TNA levels for the duration of the study, were abacteremic, exhibited no apparent signs of infection, and had no gross or microscopic lesions. However, survivors had residual spores in lung tissues. We conclude that the first two doses of the PEP schedule provide high levels of protection by the scheduled timing of the third dose. These data may also support consideration of a shorter duration PEP antimicrobial regimen.
authors.affiliation: Battelle Memorial Institute, Columbus, OH 43201, USA. Electronic address: sivkog@battelle.org.
authors.forename: G S
authors.initials: GS
authors.lastname: Sivko
authors.affiliation: Battelle Memorial Institute, Columbus, OH 43201, USA.
authors.forename: G V
authors.initials: GV
authors.lastname: Stark
authors.affiliation: Battelle Memorial Institute, Columbus, OH 43201, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Tordoff
authors.affiliation: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-9825, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Taylor
authors.affiliation: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-9825, USA.
authors.forename: E
authors.initials: E
authors.lastname: Glaze
authors.affiliation: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-9825, USA.
authors.forename: M
authors.initials: M
authors.lastname: VanRaden
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329-4027, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Schiffer
authors.affiliation: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-9825, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Hewitt
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329-4027, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Quinn
authors.affiliation: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-9825, USA.
authors.forename: E O
authors.initials: EO
authors.lastname: Nuzum
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D011897:Random Allocation; D012141:Respiratory Tract Infections / Q000517:prevention & control*; D016019:Survival Analysis; D014611:Vaccination
chemical_list: D022122:Anthrax Vaccines; D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing
keywords: Anthrax; Bacillus anthracis; BioThrax; Correlates of protection