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

Mary A. Hall, Steven D. Stroop, Mary C. Hu, Michael A. Walls, Mark A. Reddish, David S. Burt, George H. Lowell, James Dale

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2507-2512
Number of pages6
JournalInfection and Immunity
Volume72
Issue number5
DOIs
StatePublished - May 1 2004

Fingerprint

Streptococcal Vaccines
Immunization
Vaccines
Infection
Antibodies
Lipid A
Streptococcus
Liposomes
Serum
Cytokines
T-Lymphocytes
Shigella flexneri
Proteins
Neisseria meningitidis
Cholera Toxin
Intramuscular Injections
Antibody Formation
Lipopolysaccharides
Membrane Proteins
Spleen

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

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.

In: Infection and Immunity, Vol. 72, No. 5, 01.05.2004, p. 2507-2512.

Research output: Contribution to journalArticle

Hall, Mary A. ; Stroop, Steven D. ; Hu, Mary C. ; Walls, Michael A. ; Reddish, Mark A. ; Burt, David S. ; Lowell, George H. ; Dale, James. / Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections. In: Infection and Immunity. 2004 ; Vol. 72, No. 5. pp. 2507-2512.
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