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The Journal of Immunology, 2007, 179, 8372 -8380
Copyright © 2007 by The American Association of Immunologists, Inc.

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*Substance via MeSH

Mechanisms of Vaccine-Induced Protective Immunity against Coxiella burnetii Infection in BALB/c Mice1

Guoquan Zhang2, Kasi E. Russell-Lodrigue, Masako Andoh, Yan Zhang, Laura R. Hendrix and James E. Samuel

Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843

To elucidate the mechanisms of vaccine-induced protective immunity against Coxiella burnetii infection, we compared the protective efficacy and immunogenicity between formalin-inactivated phase I vaccine (PI-V) and phase II vaccine (PII-V) in BALB/c mice. PI-V generated significant protection while PII-V did not confer measurable protection. Analysis of cytokine and subclass Ab responses indicated that both PI-V and PII-V were able to induce a Th1-dominant immune response but did not identify the component of host response that distinguished their ability to induce protective immunity. Interestingly, immunoblot analysis identified a difference between PI-V and PII-V vaccinates in antigenic recognition by specific Ab isotypes. The observation that PI-LPS elicited significant protection but PII-LPS did not confer measurable protection suggests PI-LPS may play a key role in PI-V-induced protection. Adoptive transfer of either immune sera or splenocytes mediated significant protection in naive BALB/c mice, supporting the notion that both humoral and cellular immunity are important for development of protective immunity. However, the evidence that immune sera and B cells were unable to control infection while T cells conferred significant protection in SCID mice supports the hypothesis that T cell-mediated immunity is critical for host defense against C. burnetii infection. This report presents novel evidence to highlight the importance of PI-LPS and Abs in protective immunity and has important implications for the design of new generation vaccines against Q fever.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Public Health Service Grants AI057156, AI37744, and AI448191 (to J.E.S.) from the National Institute of Allergy and Infectious Diseases.

2 Address correspondence and reprint requests to Dr. Guoquan Zhang, Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114. E-mail address: gqzhang{at}medicine.tamhsc.edu

3 Abbreviations used in this paper: PI, phase I; PII, phase II; PI-V, phase I vaccine; PII-V, phase II vaccine; NMI, Nine Mile phase I; NMII, Nine Mile phase II.







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