Efficacy of recombinant anthrax vaccine against Bacillus anthracis aerosol spore challenge: preclinical evaluation in rabbits and Rhesus monkeys.
This report describes the immunogenicity and protective efficacy of Escherichia coli-expressed recombinant protective antigen (rPA) in New Zealand White rabbits and Rhesus Macaques against an aerosol challenge with Bacillus anthracis spores (IVRI strain, tox+cap+). A dose-ranging study was performed in which it became evident that the level of anti-PA IgG and toxin-neutralizing antibody titer was directly proportional to the dose of rPA administered. However, the onset time of primary and secondary immune response was not dependent on the dosage. Revaccination of primed animals with the same threshold dose yielded a robust and rapid secondary response. Quantitative differences in peak titers were obtained for both the animal models, in addition to qualitative differences in the immune kinetics. In spite of a weak priming response, the secondary response in rabbits peaked earlier than that in macaques once the booster dose was administered. However, evaluation of the post-challenge quantitative anti-rPA ELISA titer measurements indicated higher titers for non-human primates as compared to the lagomorphs. Importantly, 100% protection was seen for the dosage groups that received > or = 25 microg rPA, following a challenge against a target dose of 1000 LD(50) of aerosolized spores of Bacillus anthracis.
Chawla
Anil
A
Panacea Biotec Ltd., New Delhi, India.
Midha
Shuchi
S
Bhatnagar
Rakesh
R
D000336:Aerosols; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000737:chemistry*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D007700:Kinetics; D008253:Macaca mulatta; D009500:Neutralization Tests; D011817:Rabbits; D013171:Spores, Bacterial / Q000276:immunology*; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000627:therapeutic use*
D000336:Aerosols; D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D014614:Vaccines, Synthetic; C030325:anthrax toxin