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Infection and Immunity, October 2005, p. 6752-6762, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6752-6762.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Opsonic and Protective Activities of Staphylococcus aureus Conjugate Vaccines Containing Native or Deacetylated Staphylococcal Poly-N-Acetyl-ß-(1-6)-Glucosamine

Tomás Maira-Litrán,1* Andrea Kropec,1 Donald A. Goldmann,2 and Gerald B. Pier1

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts 02115,1 Division of Infectious Diseases, Department of Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts 021152

Received 9 February 2005/ Returned for modification 30 March 2005/ Accepted 18 May 2005

Staphylococcus aureus and Staphylococcus epidermidis both synthesize the surface polysaccharide poly-N-acetyl-ß-(1-6)-glucosamine (PNAG), which is produced in vitro with a high level (>90%) of the amino groups substituted by acetate. Here, we examined the role of the acetate substituents of PNAG in generating opsonic and protective antibodies. PNAG and a deacetylated form of the antigen (dPNAG; 15% acetylation) were conjugated to the carrier protein diphtheria toxoid (DT) and used to immunize animals. Mice responded in a dose-dependent fashion to both conjugate vaccines, with maximum antibody titers observed at the highest dose and 4 weeks after the last of three weekly immunizations. PNAG-DT and dPNAG-DT vaccines were also very immunogenic in rabbits. Antibodies raised to the conjugate vaccines in rabbits mediated the opsonic killing of various staphylococcal strains, but the specificity of the opsonic killing was primarily to dPNAG, as this antigen inhibited the killing of S. aureus strains by both PNAG- and dPNAG-specific antibodies. Passive immunization of mice with anti-dPNAG-DT rabbit sera showed significant levels of clearance of S. aureus from the blood (54 to 91%) compared to control mice immunized with normal rabbit sera, whereas PNAG-specific antibodies were ineffective at clearing S. aureus. Passive immunization of mice with a goat antiserum raised to the dPNAG-DT vaccine protected against a lethal dose of three different S. aureus strains. Overall, these data show that immunization of animals with a conjugate vaccine of dPNAG elicit antibodies that mediated opsonic killing and protected against S. aureus infection, including capsular polysaccharide types 5 and 8 and an untypable strain.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Ave., Boston, MA 02115. Phone: (617) 525-2667. Fax: (617) 525-2510. E-mail: address: tmaira{at}rics.bwh.harvard.edu.

Editor: J. N. Weiser

Infection and Immunity, October 2005, p. 6752-6762, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6752-6762.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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