Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: A randomized trial

• Authors: Jennifer G Wright, Centers for Disease Control and Prevention, Atlanta; Brian D Plikaytis, Centers for Disease Control and Prevention, Atlanta; Charles E Rose, Centers for Disease Control and Prevention, Atlanta; Scott D Parker, University of Alabama Birmingham; Janiine Babcock, Walter Reed Army Inst Res; Wendy Keitel, Baylor College of Medicine; Hana El Sahly, Baylor College of Medicine; Gregory A Poland, Mayo Clinic and Foundation; Robert M Jacobson, Mayo Clinic and Foundation; Harry Keyserling, Emory University; Vera A Semenova, Centers for Disease Control and Prevention, Atlanta; Han Li, Centers for Disease Control and Prevention, Atlanta; Jarad Schiffer, Centers for Disease Control and Prevention, Atlanta; Hanan Dababneh, Centers for Disease Control and Prevention, Atlanta; Sandra K Martin, Centers for Disease Control and Prevention, Atlanta; Stacey W Martin, Centers for Disease Control and Prevention, Atlanta; Nina Marano, Centers for Disease Control and Prevention, Atlanta; Nancy Messonnier, Emory University; Conrad P Quinn, Centers for Disease Control and Prevention, Atlanta
• Journal Title: VACCINE
• Volume: Volume 32, Number 8
• Publisher: ELSEVIER SCI LTD | 2014-02-12, Pages 1019-1028
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.vaccine.2013.10.039
• Subjects: Biology, Microbiology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; Anthrax vaccines; Bacillus anthracis; Bacterial vaccines; Vaccination; Adverse events; LETHAL TOXIN NEUTRALIZATION; SIDED TESTS PROCEDURE; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; RHESUS MACAQUES; COMPARATIVE EFFICACY; INHALATION ANTHRAX; IMMUNOGLOBULIN-G; GUINEA-PIGS; IMMUNOGENICITY

Abstract

Objective: We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Methods: Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). Results: The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months. Conclusions: A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response. © 2013 .