title: Serological Correlate of Protection in Guinea Pigs for a Recombinant Protective Antigen Anthrax Vaccine Produced from Bacillus brevis.
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.
  
  
  CONCLUSIONS
  Neutralizing-antibody titers can be used as a surrogate marker.
authors.affiliation: Division of High-risk Pathogen Research, National Institute of Health Korea National Institute of Health, Osong, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Chun
authors.forename: On-Jee
authors.initials: OJ
authors.lastname: Choi
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Cho
authors.forename: Kee-Jong
authors.initials: KJ
authors.lastname: Hong
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Seong
authors.forename: Hee-Bok
authors.initials: HB
authors.lastname: Oh
authors.forename: Gi-Eun
authors.initials: GE
authors.lastname: Rhie
keywords: Bacillus anthracis; Guinea pig; anthrax; serological correlate