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: Conrad P Quinn, Carol L Sabourin, Nancy A Niemuth, Han Li, Vera A Semenova, Thomas L Rudge, Heather J Mayfield, Jarad Schiffer, Robert S Mittler, Chris C Ibegbu, Jens Wrammert, Rafi Ahmed, April M Brys, Robert E Hunt, Denyse Levesque, James E Estep, Roy E Barnewall, David M Robinson, Brian D Plikaytis, Nina Marano, AVRP Laboratory Working Group
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 19 Issue 11 Pg. 1730-45 (Nov 2012) ISSN: 1556-679X [Electronic] United States
• PMID: 22933399 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anthrax Vaccines
• Antibodies, Bacterial
• Antibodies, Neutralizing
• Antigens, Bacterial
• Antitoxins
• Bacterial Toxins
• Immunoglobulin G
• anthrax toxin
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Anthrax (immunology, prevention & control)
• Anthrax Vaccines (administration & dosage, immunology)
• Antibodies, Bacterial (blood)
• Antibodies, Neutralizing (blood)
• Antigens, Bacterial (immunology)
• Antitoxins (blood)
• B-Lymphocytes (immunology)
• Bacterial Toxins (immunology)
• Cell Proliferation
• Disease Models, Animal
• Immunoglobulin G (blood)
• Injections, Intramuscular
• Interferon-gamma (metabolism)
• Interleukin-4 (metabolism)
• Macaca mulatta
• Respiratory Tract Infections (immunology, prevention & control)
• T-Lymphocytes (immunology)
• Time Factors
• Vaccination (methods)