title: A three-dose intramuscular injection schedule of anthrax vaccine adsorbed generates sustained humoral and cellular immune responses to protective antigen and provides long-term protection against inhalation anthrax in rhesus macaques.
abstract: A 3-dose (0, 1, and 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions of up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. Serum anti-protective antigen (anti-PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA or following two injections of diluted vaccine (1:10, 1:20, or 1:40 AVA). Anti-PA and TNA were highly correlated (overall r(2) = 0.89 for log(10)-transformed data). Peak responses were seen at 6.5 months. In general, with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5 months (the last time point measured for 1:20 AVA), and through 50.5 months for the HuAVA and 1:5 and 1:10 AVA groups (P < 0.05). PA-specific gamma interferon (IFN-γ) and interleukin-4 (IL-4) CD4(+) cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA. cquinn@cdc.gov
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Quinn
authors.forename: Carol L
authors.initials: CL
authors.lastname: Sabourin
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Niemuth
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Vera A
authors.initials: VA
authors.lastname: Semenova
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rudge
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Mayfield
authors.forename: Jarad
authors.initials: J
authors.lastname: Schiffer
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mittler
authors.forename: Chris C
authors.initials: CC
authors.lastname: Ibegbu
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: April M
authors.initials: AM
authors.lastname: Brys
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hunt
authors.forename: Denyse
authors.initials: D
authors.lastname: Levesque
authors.forename: James E
authors.initials: JE
authors.lastname: Estep
authors.forename: Roy E
authors.initials: RE
authors.lastname: Barnewall
authors.forename: David M
authors.initials: DM
authors.lastname: Robinson
authors.forename: Brian D
authors.initials: BD
authors.lastname: Plikaytis
authors.forename: Nina
authors.initials: N
authors.lastname: Marano
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood*; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D000992:Antitoxins / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008253:Macaca mulatta; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods*
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D007074:Immunoglobulin G; C030325:anthrax toxin; D015847:Interleukin-4; D007371:Interferon-gamma