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

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 seru...

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Main Authors: Hall, Mary A., Stroop, Steven D., Hu, Mary C., Walls, Michael A., Reddish, Mark A., Burt, David S., Lowell, George H., Dale, James B.
Formato: Artigo
Idioma:en
Publicado em: American Society for Microbiology 2004
Assuntos:
Microbial Immunity and Vaccines
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC387888/
https://ncbi.nlm.nih.gov/pubmed/15102757
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/IAI.72.5.2507-2512.2004
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spelling pubmed-3878882004-05-14 Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections Hall, Mary A. Stroop, Steven D. Hu, Mary C. Walls, Michael A. Reddish, Mark A. Burt, David S. Lowell, George H. Dale, James B. Infect Immun Microbial Immunity and Vaccines 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. American Society for Microbiology 2004-05 /pmc/articles/PMC387888/ /pubmed/15102757 http://dx.doi.org/10.1128/IAI.72.5.2507-2512.2004 Text en Copyright © 2004, American Society for Microbiology
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Microbial Immunity and Vaccines
spellingShingle Microbial Immunity and Vaccines
Hall, Mary A.
Stroop, Steven D.
Hu, Mary C.
Walls, Michael A.
Reddish, Mark A.
Burt, David S.
Lowell, George H.
Dale, James B.
Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
description 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.
author Hall, Mary A.
Stroop, Steven D.
Hu, Mary C.
Walls, Michael A.
Reddish, Mark A.
Burt, David S.
Lowell, George H.
Dale, James B.
author_facet Hall, Mary A.
Stroop, Steven D.
Hu, Mary C.
Walls, Michael A.
Reddish, Mark A.
Burt, David S.
Lowell, George H.
Dale, James B.
author_sort Hall, Mary A.
title Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
title_short Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
title_full Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
title_fullStr Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
title_full_unstemmed Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections
title_sort intranasal immunization with multivalent group a streptococcal vaccines protects mice against intranasal challenge infections
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2004
url https://ncbi.nlm.nih.gov/pmc/articles/PMC387888/
https://ncbi.nlm.nih.gov/pubmed/15102757
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/IAI.72.5.2507-2512.2004
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