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Infection and Immunity, April 2002, p. 2171-2177, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2171-2177.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immunogenicity of a 26-Valent Group A Streptococcal Vaccine

Mary C. Hu,1 Michael A. Walls,1 Steven D. Stroop,1 Mark A. Reddish,1 Bernard Beall,2 and James B. Dale3*

ID Biomedical Corporation, Bothell, Washington,1 Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia,2 Department of Veterans Affairs Medical Center and Department of Medicine, University of Tennessee, Memphis, Tennessee3

Received 12 November 2001/ Returned for modification 19 December 2001/ Accepted 18 January 2002

A multivalent vaccine containing amino-terminal M protein fragments from 26 different serotypes of group A streptococci was constructed by recombinant techniques. The vaccine consisted of four different recombinant proteins that were formulated with alum to contain 400 µg of protein per dose. Rabbits were immunized via the intramuscular route at 0, 4, and 16 weeks. Immune sera were assayed for the presence of type-specific antibodies against the individual recombinant M peptides by enzyme-linked immunosorbent assay and for opsonic antibodies by in vitro opsonization tests and indirect bactericidal tests. The 26-valent vaccine was highly immunogenic and elicited fourfold or greater increases in antibody levels against 25 of the 26 serotypes represented in the vaccine. The immune sera were broadly opsonic and were bactericidal against the majority of the 26 different serotypes. Importantly, none of the immune sera cross-reacted with human tissues. Our results indicate that type-specific, protective M protein epitopes can be incorporated into complex, multivalent vaccines designed to elicit broadly protective opsonic antibodies in the absence of tissue-cross-reactive antibodies.

* Corresponding author. Mailing address: VA Medical Center (11A), University of Tennessee, 1030 Jefferson Ave., Memphis, TN 38104. Phone: (901) 577-7207. Fax: (901) 448-8231. E-mail: james.dale{at}med.va.gov.

Editor: E. I. Tuomanen

Infection and Immunity, April 2002, p. 2171-2177, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2171-2177.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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Copyright © 2002 by the American Society for Microbiology. All rights reserved.