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Infection and Immunity, August 2002, p. 4600-4608, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4600-4608.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Quantitative Priming with Inactivated Pertussis Toxoid Vaccine in the Aerosol Challenge Model

Jon B. Bruss* and George R. Siber,{dagger}

Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts

Received 31 October 2001/ Returned for modification 22 January 2002/ Accepted 11 April 2002

Serum antibodies to pertussis toxin (PT) have been shown to be protective against severe pertussis disease, although a specific level of anti-PT antibody that correlates with protection has not been demonstrated. Current animal models such as the intracerebral challenge model have significant limitations in correlating protection to a specific level of anti-PT antibody. This study examines the protective effects of priming with tetranitromethane-inactivated pertussis toxoid (PTx) vaccine in the aerosol challenge model and whether a measurable response to a priming dose of PTx is enough to initiate a protective secondary response when challenged with infection. The correlation of priming with markers of illness such as leukocytosis, weight loss, bacterial proliferation, and mortality after established infection with Bordetella pertussis was explored. BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. Data were analyzed according to the primary immunologic response, differentiating responders (anti-PT immunoglobulin G [IgG] >=1 µg/ml) from nonresponders (anti-PT IgG <1 µg/ml). Mice that showed evidence of priming on the day of aerosol challenge were able to mount a secondary response to the challenge with a >=2-fold rise in anti-PT IgG antibody by day 7 and a >=10-fold rise by day 14 post-aerosol challenge. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge.

* Corresponding author. Present address: Clinical Research-Infectious Diseases, Pharmacia Corporation, 7000 Portage Rd., Kalamazoo, MI 49001. Phone: (616) 833-8714. Fax: (616) 833-0203. E-mail: jon.b.bruss{at}pharmacia.com.

Editor: R. N. Moore

{dagger} Present address: Wyeth-Lederle Vaccines, Pearl River, N.Y.

Infection and Immunity, August 2002, p. 4600-4608, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4600-4608.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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