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Infection and Immunity, May 2004, p. 2507-2512, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2507-2512.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections

Mary A. Hall,1 Steven D. Stroop,2 Mary C. Hu,2 Michael A. Walls,2 Mark A. Reddish,2 David S. Burt,3 George H. Lowell,3 and James B. Dale1*

Department of Veterans Affairs Medical Center and the Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee,1 ID Biomedical Corporation of Washington, Bothell, Washington,2 ID Biomedical Corporation of Quebec, Montreal, Quebec, Canada3

Received 14 November 2003/ Returned for modification 2 January 2004/ Accepted 16 January 2004

We have previously shown that a hexavalent group A streptococcal M protein-based vaccine evoked bactericidal antibodies after intramuscular injection. In the present study, we show that the hexavalent vaccine formulated with several different mucosal adjuvants and delivered intranasally induced serum and salivary antibodies that protected mice from intranasal challenge infections with virulent group A streptococci. The hexavalent vaccine was formulated with liposomes with or without monophosphorylated lipid A (MPL), cholera toxin B subunit with or without holotoxin, or proteosomes from Neisseria meningitidis outer membrane proteins complexed with lipopolysaccharide from Shigella flexneri. Intranasal immunization with the hexavalent vaccine mixed with these adjuvants resulted in significant levels of antibodies in serum 2 weeks after the final dose. Mean serum antibody titers were equivalent in all groups of mice except those that were immunized with hexavalent protein plus liposomes without MPL, which were significantly lower. Salivary antibodies were also detected in mice that received the vaccine formulated with the four strongest adjuvants. T-cell proliferative assays and cytokine assays using lymphocytes from cervical lymph nodes and spleens from mice immunized with the hexavalent vaccine formulated with proteosomes indicated the presence of hexavalent protein-specific T cells and a Th1-weighted mixed Th1-Th2 cytokine profile. Intranasal immunization with adjuvanted formulations of the hexavalent vaccine resulted in significant levels of protection (80 to 100%) following intranasal challenge infections with type 24 group A streptococci. Our results indicate that intranasal delivery of adjuvanted multivalent M protein vaccines induces protective antibody responses and may provide an alternative to parenteral vaccine formulations.

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

Editor: D. L. Burns

Infection and Immunity, May 2004, p. 2507-2512, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2507-2512.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tewodros, W., Kronvall, G. (2005). M Protein Gene (emm Type) Analysis of Group A Beta-Hemolytic Streptococci from Ethiopia Reveals Unique Patterns. J. Clin. Microbiol. 43: 4369-4376 [Abstract] [Full Text]  
  • Gladstone, P., Varghese, G., Brahmadathan, K N (2005). Dynamics of anti-M antibody response in a mouse model following intranasal infection with group A Streptococcus M-18. J Med Microbiol 54: 305-308 [Abstract] [Full Text]  


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