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Infection and Immunity, May 2001, p. 2888-2893, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2888-2893.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Search for Correlates of Protective Immunity Conferred by Anthrax Vaccine

Shaul Reuveny,1 Moshe D. White,1 Yaakov Y. Adar,1 Yaron Kafri,1 Zeev Altboum,2 Yehusha Gozes,2 David Kobiler,2 Avigdor Shafferman,3 and Baruch Velan3,*

Departments of Biotechnology,1 Infectious Diseases,2 and Biochemistry and Molecular Genetics,3 Israel Institute for Biological Research, Ness-Ziona 74100, Israel

Received 30 November 2000/Returned for modification 3 January 2001/Accepted 30 January 2001

Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens. In spite of the vast use of PA-based vaccines, the definition of a marker for protective immunity is still lacking. Here we describe studies designed to help define such markers. To this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of protection against a lethal challenge with anthrax spores. Active immunization was performed by a single injection using one of two methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with constant amounts of PA that had been thermally inactivated for increasing periods. In both studies a direct correlation between survival and neutralizing-antibody titer was found (r2 = 0.92 and 0.95, respectively). Most significantly, in the two protocols a similar neutralizing-antibody titer range provided 50% protection. Furthermore, in a complementary study involving passive transfer of PA hyperimmune sera to naive animals, a similar correlation between neutralizing-antibody titers and protection was found. In all three immunization studies, neutralization titers of at least 300 were sufficient to confer protection against a dose of 40 50% lethal doses (LD50) of virulent anthrax spores of the Vollum strain. Such consistency in the correlation of protective immunity with anti-PA antibody titers was not observed for antibody titers determined by an enzyme-linked immunosorbent assay. Taken together, these results clearly demonstrate that neutralizing antibodies to PA constitute a major component of the protective immunity against anthrax and suggest that this parameter could be used as a surrogate marker for protection.

* Corresponding author: Mailing address: P.O. Box 19, 74100 Ness-Ziona, Israel. Phone: 972-8-9381518. Fax: 972-8-9401404. E-mail: baruch{at}iibr.gov.il.

Infection and Immunity, May 2001, p. 2888-2893, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2888-2893.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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