Duration of protection of rabbits after vaccination with Bacillus anthracis recombinant protective antigen vaccine☆

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

“…Significant durability of neutralization was also observed, as reflected in the increase in neutralization titers for rabbits MR4 and MR6 between their eighth and final injection and their terminal bleeds 2.5 months later. We considered the potential role of Freund's adjuvant, a water-in-oil emulsion, in explaining this finding; however, we have not seen this effect in rabbits immunized with PA in Freund's adjuvant, where, more typically, we have observed significant diminution in LeTx neutralization by 4 to 6 weeks after the final immunization, a pattern also seen with rabbits immunized with PA formulated with other adjuvants (26,27). The evidence, instead, suggests that the durability more likely results from the use of the MAP peptide, a form of immunogen which has been shown by others to be capable of eliciting highly durable antibody responses (59).…”

“…This assay evaluates the functional ability of antibody to neutralize LeTx in vitro, and TNA titers have been shown to correlate well with protection in inhalation spore challenges (19,26,27,46). The MAP-immune serum exhibited neutralization of LeTx at levels equivalent to those in the sera of the two positive-control rabbits, even though the PA-specific antibody titer in the serum of this MAP-immune rabbit was less than 15% of those for the control PA-immune rabbits (Fig.…”

“…Among the three other responder rabbits, the peak levels of neutralization were 100%, 67%, and 41% of those for the PA-immune control rabbits. Though neutralization is considered the best in vitro surrogate for vaccine efficacy in aerosol spore challenges in rabbits, there is overlap in the ranges of neutralization titers which are associated with survivors and nonsurvivors (19,26,27,38,46). Nevertheless, PA-specific responses with neutralization titers exceeding 750 to 1,000 appear predictive of protection.…”

Effect of aluminum hydroxide adjuvant and formaldehyde in the formulation of rPA anthrax vaccine

“…Studies that had been conducted in evaluating rPA vaccine preparations, including serological correlates of immunity in rabbits [15], potency assay [28], and duration of immunity in rabbits [29], were not formulated with components other than aluminum hydroxide gel adjuvant. The serological response and efficacy of vaccines containing 50 g of rPA adsorbed to Alhydrogel (500 g of aluminum) and formulated either with 0.02% formaldehyde 50 titer could not be extrapolated from the four-parameter logistic regression curve, the value was arbitrarily assigned a value of '1.0'.…”

Validation of an Anti-Protective Antigen ELISA for Quantitative IgG Evaluation in B. anthracis Immunized Horses

“…We have developed an anti-PA IgG ELISA designed to measure the immune response against PA in horses. This assay was developed using the validation parameters suggested by the ICH and CBER and is consistent with other literature where serologic assays have been used to verify immunologic responses and vaccine analyses [23][24][25]. Acceptance criteria for the validation of this assay were based on the performance of similar ELISAs [15,26].…”