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Infection and Immunity, August 2005, p. 5031-5038, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.5031-5038.2005

Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits

David R. Shoemaker,{dagger} Nancy B. Saunders,{ddagger} Brenda L. Brandt, E. Ellen Moran, Andrew D. LaClair, and Wendell D. Zollinger*

Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500

Received 9 February 2005/ Returned for modification 25 February 2005/ Accepted 11 March 2005

We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal immunization of humans. Rabbits immunized intranasally with doses of 100 µg of NOMV in 0.5 ml of saline developed serum bactericidal antibody levels comparable to those of rabbits immunized intramuscularly with 25-µg doses, particularly when the primary intranasal immunization was given daily for 3 days. Intranasal immunization also induced a local mucosal response as evidenced by immunoglobulin A antibody in saliva, nasal washes, and lung lavage fluids. NOMV from a capsule-deficient mutant induced higher serum bactericidal antibody responses than NOMV from the encapsulated parent. Meningococcal NOMV could be administered intranasally at 400 µg with no pyrogenic activity, but as little as 0.03 µg/kg of body weight administered intravenously or 25 µg administered intramuscularly induced a pyrogenic response. These data indicate that the rabbit is a useful model for preclinical testing of intranasal meningococcal NOMV vaccines, and this immunization regimen produces a safe and substantial systemic and local mucosal antibody response.

* Corresponding author. Mailing address: Department of Bacterial Diseases, WRAIR, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500. Phone: (301) 319-9901. Fax: (301) 319-9123. E-mail: wendell.zollinger{at}na.amedd.army.mil.

Editor: J. N. Weiser

{dagger} Present address: United States Army Medical Materiel Development Activity, Fort Detrick, Maryland.

{ddagger} Present address: National Institutes of Health, Bethesda, Maryland.

Infection and Immunity, August 2005, p. 5031-5038, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.5031-5038.2005






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