title: Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans.
abstract: Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti-PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-γ)- and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-γ, IL-2, IL-4, IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1-Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7,r(2)= 0.86,P< 0.0001, log10 transformed) and declined in the absence of boosters. Boosters administered IM generated the highest antibody responses. Increasing time intervals between boosters generated antibody responses that were faster than and superior to those obtained with the final month 42 vaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. NCT00119067.).
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA cquinn@cdc.gov.
authors: Conrad P
authors: CP
authors: Quinn
authors: Battelle, Columbus, Ohio, USA.
authors: Carol L
authors: CL
authors: Sabourin
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Jarad M
authors: JM
authors: Schiffer
authors: Battelle, Columbus, Ohio, USA.
authors: Nancy A
authors: NA
authors: Niemuth
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Vera A
authors: VA
authors: Semenova
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Han
authors: H
authors: Li
authors: Battelle, Columbus, Ohio, USA.
authors: Thomas L
authors: TL
authors: Rudge
authors: Battelle, Columbus, Ohio, USA.
authors: April M
authors: AM
authors: Brys
authors: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA Yerkes National Primate Center, Emory University, Atlanta, Georgia, USA.
authors: Robert S
authors: RS
authors: Mittler
authors: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA Yerkes National Primate Center, Emory University, Atlanta, Georgia, USA.
authors: Chris C
authors: CC
authors: Ibegbu
authors: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
authors: Jens
authors: J
authors: Wrammert
authors: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
authors: Rafi
authors: R
authors: Ahmed
authors: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Scott D
authors: SD
authors: Parker
authors: Walter Reed Army Institute for Research, Silver Spring, Maryland, USA.
authors: Janiine
authors: J
authors: Babcock
authors: Baylor College of Medicine, Houston, Texas, USA.
authors: Wendy
authors: W
authors: Keitel
authors: Mayo Clinic, Rochester, Minnesota, USA.
authors: Gregory A
authors: GA
authors: Poland
authors: Emory University School of Medicine, Atlanta, Georgia, USA.
authors: Harry L
authors: HL
authors: Keyserling
authors: Baylor College of Medicine, Houston, Texas, USA.
authors: Hana
authors: H
authors: El Sahly
authors: Mayo Clinic, Rochester, Minnesota, USA.
authors: Robert M
authors: RM
authors: Jacobson
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Nina
authors: N
authors: Marano
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Brian D
authors: BD
authors: Plikaytis
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Jennifer G
authors: JG
authors: Wright
mesh_terms: D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D009500:Neutralization Tests; D010919:Placebos / Q000008:administration & dosage
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D007074:Immunoglobulin G; D010919:Placebos; C030325:anthrax toxin