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Multivalent Group A Streptococcal Vaccine Elicits Bactericidal Antibodies against Variant M Subtypes

Department of Veterans Affairs, and,¹ Department of Medicine,² Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, Tennessee,³ Department of Pediatrics, Feinberg School of Medicine, Northwestern University, and Division of Infectious Diseases, Children's Memorial Hospital, Chicago, Illinois,⁴ Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia⁵

Received 17 February 2005/ Returned for modification 18 April 2005/ Accepted 27 April 2005

Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.