Efficacy of recombinant anthrax vaccine against Bacillus anthracis aerosol spore challenge: Preclinical evaluation in rabbits and Rhesus monkeys

Abstract

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.

Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA- (High Temperature Requirement A) Sterne Strain

“…Therefore, this response addresses both toxaemia and the bacteremia, which are both associated with B. anthracis infection. Of note, full-protection of rabbits vaccinated with a PA sub-unit vaccine correlates with at least 3-fold higher levels of neutralizing antibodies 39 40 compared to the antibodies in the fully protected animals following SterneΔ htrA vaccination. Similarly, in the guinea pig immunization experiments ( Fig.…”

Anthrax Vaccine–Induced Antibodies Provide Cross-Species Prediction of Survival to Aerosol Challenge

“…Both vaccines rely largely on the protection afforded by immunological responses against the PA protein [14–20]. Many studies have shown the protective efficacy of PA based anthrax vaccines in several animal genera and species including guinea pigs [21–25], rabbits [26–29] and NHPs [20, 26, 30–33]. A few studies have gone further to evaluate correlate of protection levels based on antibody to PA for AVA in rabbits [28, 29] and for rPA in rabbits [27] and guinea pigs [25].…”

A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys

“…Additionally, as a single, well-defined, recombinant protein, rPA represents an attractive antigen alternative to that found in AVA, which while containing predominantly PA absorbed to alum, also contains other antigens and is of undefined composition with lot to lot variation (38). A number of studies in monkeys, a suitable surrogate for predicting the human anthrax vaccine response (39), have shown complete protection against lethal aerosolized anthrax challenge following a 2–3 immunization regimen of AVA or rPA on alum (39–42), but complete protection following a single immunization has yet to be demonstrated in these animals. Thus, the ability of CpG-ODN to promote rapid, high titer and durable antibody responses to antigens makes this class of adjuvant a strong candidate for improving the rapidity and magnitude of antibody responses to vaccines against potential biological warfare agents such as anthrax.…”