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Infection and Immunity, September 2005, p. 5978-5987, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5978-5987.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Immunogenicity of Recombinant Protective Antigen and Efficacy against Aerosol Challenge with Anthrax

E. D. Williamson,1* I. Hodgson,1 N. J. Walker,1 A. W. Topping,2 M. G. Duchars,2 J. M. Mott,3 J. Estep,3 C. LeButt,1 H. C. Flick-Smith,1 H. E. Jones,1 H. Li,4 and C. P. Quinn4

Defence Science and Technology Laboratory Porton Down, Salisbury, Wilts. SP4 0JQ, United Kingdom,1 Avecia Biotechnology, Billingham, Cleveland, TS23 1YN, United Kingdom,2 Battelle Medical Research and Evaluation Facility, Columbus, Ohio,3 Centers for Disease Control and Prevention, Atlanta, Georgia4

Received 11 March 2005/ Returned for modification 4 May 2005/ Accepted 15 May 2005

Immunization with a recombinant form of the protective antigen (rPA) from Bacillus anthracis has been carried out with rhesus macaques. Rhesus macaques immunized with 25 µg or more of B. subtilis-expressed rPA bound to alhydrogel had a significantly increased immunoglobulin G (IgG) response to rPA compared with macaques receiving the existing licensed vaccine from the United Kingdom (anthrax vaccine precipitated [AVP]), although the isotype profile was unchanged, with bias towards the IgG1 and IgG2 subclasses. Immune macaque sera from all immunized groups contained toxin-neutralizing antibody and recognized all the domains of PA. While the recognition of the N terminus of PA (domains 1 to 3) was predominant in macaques immunized with the existing vaccines (AVP and the U.S. vaccine anthrax vaccine adsorbed), macaques immunized with rPA recognized the N- and C-terminal domains of PA. Antiserum derived from immunized macaques protected macrophages in vitro against the cytotoxic effects of lethal toxin. Passive transfer of IgG purified from immune macaque serum into naive A/J mice conferred protection against challenge with B. anthracis in a dose-related manner. The protection conferred by passive transfer of 500 µg macaque IgG correlated significantly (P = 0.003; r = 0.4) with the titers of neutralizing antibody in donor macaques. Subsequently, a separate group of rhesus macaques immunized with 50 µg of Escherichia coli-derived rPA adsorbed to alhydrogel was fully protected against a target dose of 200 50% lethal doses of aerosolized B. anthracis. These data provide some preliminary evidence for the existence of immune correlates of protection against anthrax infection in rhesus macaques immunized with rPA.

* Corresponding author. Mailing address: Defence Science and Technology Laboratory Porton Down, Salisbury, Wilts. SP4 0JQ, United Kingdom. Phone: 44 1980 613895. Fax: 44 1980 614307. E-mail: dewilliamson{at}dstl.gov.uk.

Editor: J. D. Clements

Infection and Immunity, September 2005, p. 5978-5987, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5978-5987.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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