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Author Notes:

Address correspondence to Conrad P. Quinn, cquinn@cdc.gov.

We acknowledge J. Wright, N. Messonnier, D. Ashford, J. Lingappa, J. Caba, and J. Walls for their contributions.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Subject:

Research Funding:

This study was funded through the Centers for Disease Control and Prevention, Atlanta, GA. The Battelle Biomedical Research Center was funded under DHHS CDC contract 200-2000-10065.

The members of the AVRP Laboratory Working Group marked by asterisks were funded by the Atlanta Research and Education Foundation (AREF) through the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Atlanta, GA.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Infectious Diseases
  • Microbiology
  • IMMUNOLOGY
  • INFECTIOUS DISEASES
  • MICROBIOLOGY
  • RECEPTOR-BINDING REGION
  • IN-VITRO CORRELATE
  • CD4(+) T-CELLS
  • BACILLUS-ANTHRACIS
  • LETHAL FACTOR
  • MONOCLONAL-ANTIBODIES
  • PASSIVE PROTECTION
  • GUINEA-PIGS
  • NEUTRALIZING ANTIBODIES
  • TOXIN COMPONENTS

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

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Journal Title:

Clinical and Vaccine Immunology

Volume:

Volume 19, Number 11

Publisher:

, Pages 1730-1745

Type of Work:

Article | Final Publisher PDF

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 log10-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. Copyright

Copyright information:

© 2012, American Society for Microbiology. All Rights Reserved.

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