Intranasal immunization with multivalent group A streptococcal vaccines protects mice against intranasal challenge infections.

Abstract

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.

• Authors: Mary A Hall, Steven D Stroop, Mary C Hu, Michael A Walls, Mark A Reddish, David S Burt, George H Lowell, James B Dale
• Journal: Infection and immunity (Infect Immun) Vol. 72 Issue 5 Pg. 2507-12 (May 2004) ISSN: 0019-9567 [Print] United States
• PMID: 15102757 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Proteins
• Cytokines
• Liposomes
• Streptococcal Vaccines

Topics

• Adjuvants, Immunologic (administration & dosage)
• Administration, Intranasal
• Animals
• Antibodies, Bacterial (biosynthesis, blood)
• Antibody Specificity
• Antibody-Producing Cells (immunology)
• Antigens, Bacterial
• Bacterial Proteins (immunology)
• Cytokines (biosynthesis)
• Female
• In Vitro Techniques
• Liposomes
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Saliva (immunology)
• Streptococcal Infections (immunology, prevention & control)
• Streptococcal Vaccines (administration & dosage)
• Streptococcus pyogenes (immunology)
• T-Lymphocytes (immunology)