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Infection and Immunity, December 2005, p. 8256-8265, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8256-8265.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of the Neisseria meningitidis Serogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan

Zhiming Huo,1 Ruchi Sinha,1 Edel A. McNeela,2 Ray Borrow,3 Rafaela Giemza,1 Catherine Cosgrove,1 Paul T. Heath,1 Kingston H. G. Mills,2 Rino Rappuoli,4 George E. Griffin,1 and David J. M. Lewis1*

St. George's Vaccine Institute, London, United Kingdom,1 Immune Regulation Research Group, Department of Biochemistry, Trinity College, Dublin, Ireland,2 Vaccine Evaluation Department, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, United Kingdom,3 Chiron Vaccines, Via Fiorentina, Siena, Italy4

Received 29 June 2005/ Returned for modification 4 September 2005/ Accepted 22 September 2005

Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis serogroup C polysaccharide (MCP)-CRM197 conjugate vaccine in alum or two nasal insufflations 28 days apart of the same vaccine powder, without alum, mixed with chitosan. Nasal immunization was well tolerated, with fewer symptoms reported than after intramuscular injection. The geometric mean concentrations of MCP-specific immunoglobulin G (IgG) after one nasal immunization were 3.25 µg/ml in naïve subjects and 14.4 µg/ml in subjects previously immunized parenterally, compared with 4.30 µg/ml in naïve subjects immunized intramuscularly. The geometric mean titer of serum bactericidal antibody (SBA) rose 24-fold after two nasal immunizations in naïve subjects and was comparable to parenteral immunization (1,080 versus 1,625). All subjects achieved SBA titers associated with protection after two nasal immunizations: even those with titers of <8 at entry. A single nasal immunization boosted the SBA titer to ≥128 in 96% of previously immunized subjects, and two immunizations achieved this level in 92% of naive subjects. MCP-specific IgG levels were ~70% IgG2 and ~20% IgG1 after nasal or intramuscular immunization. Increases in CRM197-specific IgG and diphtheria toxin-neutralizing activity were observed after nasal or intramuscular immunization, with balanced IgG1/IgG2 and higher IgG4. Significant MCP-specific secretory IgA was detected in nasal wash only after nasal immunization and predominantly on the immunized side. Simple nasal insufflation of existing MCP-CRM197 conjugate vaccines in chitosan offers an inexpensive but effective needle-free prime and boost against serogroup C N. meningitidis and diphtheria.

* Corresponding author. Mailing address: Centre for Infection, St. George's, London SW17 0RE, United Kingdom. Phone: 44 2087255826. Fax: 44 2087253487. E-mail: d.lewis{at}sgul.ac.uk.

Editor: J. D. Clements

Infection and Immunity, December 2005, p. 8256-8265, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8256-8265.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cross, A. S., Chen, W. H., Levine, M. M. (2008). A case for immunization against nosocomial infections. J. Leukoc. Biol. 83: 483-488 [Abstract] [Full Text]  
  • Findlow, H., Southern, J., Mabey, L., Balmer, P., Heyderman, R. S., Auckland, C., Morris, R., Miller, E., Borrow, R. (2006). Immunoglobulin G Subclass Response to a Meningococcal Quadrivalent Polysaccharide-Diphtheria Toxoid Conjugate Vaccine. CVI 13: 507-510 [Abstract] [Full Text]  


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