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* Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642;
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642; and
Infectious Disease Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642
Vaccination to generate protective humoral immunity against infectious disease is becoming increasingly important due to emerging strains of virus, poorly immunogenic vaccines, and the threat of bioterrorism. We demonstrate that cyclooxygenase-2 (Cox-2) is crucial for optimal Ab responses to a model vaccine, human papillomavirus type 16 virus-like particles (HPV 16 VLPs). Cox-2-deficient mice produce 70% less IgG, 50% fewer Ab-secreting cells, and 10-fold less neutralizing Ab to HPV 16 VLP vaccination compared with wild-type mice. The reduction in Ab production by Cox-2–/– mice was partially due to a decrease in class switching. SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by 
70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells. The widespread use of nonsteroidal anti-inflammatory drugs and Cox-2-selective inhibitory drugs may therefore reduce vaccine efficacy, especially when vaccines are poorly immunogenic or the target population is poorly responsive to immunization.
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 National Institutes of Health Grants DE011390, AI071064, and ES01247, the Toxicology Training Grant T3ES07026, the Microbiology and Immunology Training Grant T32AI007169 and R25CA102618.
2 Address correspondence and reprint requests to Dr. Richard P. Phipps, Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Box 850, Medical Research Building-X 3-11001, 601 Elmwood Avenue, Rochester, NY 14642. E-mail address: Richard_Phipps{at}urmc.rochester.edu
3 Abbreviations used in this paper: HPV, human papillomavirus; VLP, virus-like particle; Cox, cyclooxygenase; NSAID, nonsteroidal anti-inflammatory drug; SAC, Staphylococcus aureus Cowen; ASC, Ab-secreting cell.
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