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Author Notes:

J.G. Wright, National Center for Emerging Zoonotic and Infectious Diseases, Division of Foodborne, Waterborne and Environmental Diseases, 1600 Clifton Road NE, MS A-38, Atlanta, GA 30333, United States. Tel.: +1 404 639 4749. Email: jgwright@cdc.gov

Wright, Plikaytis, Rose and Quinn had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Plikaytis, Babcock, Keitel, Poland, Keyserling, Marano, Martin SW, Messonnier and Quinn. Acquisition of data: Wright, Rose, Schiffer, Semenova, Li, Marano, Parker, Babcock, Keitel, El Sahly, Poland, Jacobson, Keyserling, and Quinn. Analysis and interpretation of data: Wright, Plikaytis, Rose, Schiffer, Semenova, Li, Parker, Babcock, Keitel, El Sahly, Poland, Jacobson, Keyserling, Marano, Messonnier, Quinn. Drafting of the manuscript: Wright, Martin SW, Plikaytis, Rose, Messonnier and Quinn. Critical revision of the manuscript for important intellectual content: Wright, Plikaytis, Messonnier, Parker, Babcock, Keitel, El Sahly, Poland, Jackson, Keyserling, Quinn. Statistical analysis: Plikaytis, Rose. Administrative, technical, or material support: Wright, Parker, Babcock, Keitel, El Sahly, Poland, Jacobson, Keyserling, Dababneh, Semenova, Martin SK, Li, Schiffer and Quinn. Study supervision: Wright, Parker, Babcock, Keitel, El Sahly, Poland, Jacobson, Keyserling and Quinn.

No financial conflicts were reported for any author.

Subjects:

Research Funding:

The study was funded through the Centers for Disease Control and Prevention (CDC).

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

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

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Journal Title:

VACCINE

Volume:

Volume 32, Number 8

Publisher:

, Pages 1019-1028

Type of Work:

Article | Post-print: After Peer Review

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 .

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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