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. 2012 Sep;3(3):170-6.
doi: 10.1016/j.phrp.2012.07.006.

Serological Correlate of Protection in Guinea Pigs for a Recombinant Protective Antigen Anthrax Vaccine Produced from Bacillus brevis

Jeong-Hoon Chun  1 , On-Jee Choi, Min-Hee Cho, Kee-Jong Hong, Won Keun Seong, Hee-Bok Oh, Gi-Eun Rhie
Affiliations

Serological Correlate of Protection in Guinea Pigs for a Recombinant Protective Antigen Anthrax Vaccine Produced from Bacillus brevis

Jeong-Hoon Chun et al. Osong Public Health Res Perspect. 2012 Sep.

Abstract

Objective: Recombinant protective antigen (rPA) is the active pharmaceutical ingredient of a second generation anthrax vaccine undergoing clinical trials both in Korea and the USA. By using the rPA produced from Bacillus brevis pNU212 expression system, correlations of serological immune response to anthrax protection efficacy were analyzed in a guinea pig model.

Methods: Serological responses of rPA anthrax vaccine were investigated in guinea pigs that were given single or two injections (interval of 4 weeks) of various amounts of rPA combined with aluminumhydroxide adjuvant. Guinea pigs were subsequently challenged by the intramuscular injection with 30 half-lethal doses (30LD50) of virulent Bacillus anthracis spores. Serumantibody titerswere determined by anti-PA IgGELISA and the ability of antibodies to neutralize the cytotoxicity of lethal toxin on J774A.1 cell was measured through the toxin neutralizing antibody (TNA) assay.

Results: To examine correlations between survival rate and antibody titers, correlation between neutralizing antibody titers and the extent of protection was determined. Toxin neutralization titers of at least 1176 were sufficient to confer protection against a dose of 30LD50 of virulent anthrax spores of the H9401 strain. Such consistency in the correlation was not observed from those antibody titers determined by ELISA.

Conclusion: Neutralizing-antibody titers can be used as a surrogate marker.

Keywords: Bacillus anthracis; Guinea pig; anthrax; serological correlate.

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Figures

Figure 1.
Figure 1.. Relationship between survivals of guinea pig with a single injection of rPA vaccine after i.m. challenge with B anthracis H9401 spore and Week 3. (A) Anti-PA IgG titer, (B) ED50 TNA assay. Guinea pigs (●) surviving or (○) dying after i.m. injection.
Figure 2.
Figure 2.. Relationship between survivals of guinea pig inoculated with two injection of rPA vaccine after i.m. challenge with B. anthracis H9401 spore and Week 7. (A) Anti-PA IgG titer; (B) ED50 TNA assay. Guinea pigs (◆) surviving or (◇) dying after i.m. injection.
Figure 3.
Figure 3.. Correlation between TNA titers and protection after two injections. Relationship between serological titer and protection of guinea pigs with a double vaccination serially diluted of rPA vaccine at a 4-week interval. After 4 weeks after the second vaccination, guinea pigs were challenged i.m with B anthracis H9401 spores. Each point in the group represents the average of duplicate determinations performed with pooled sera derived from 9 or 10 guinea pigs. TNA titers of serum samples from individual animals in each group were compared to the survival data of the animals (inset). Linear regression was performed using data from experimental cohorts with neutralizing-antibody titers of 1176 or less. The calculated R2 value is 0.96.
See this image and copyright information in PMC

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