Cyclooxygenase-2 inhibition attenuates antibody responses against human papillomavirus-like particles.
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 approximately 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.
Ryan
Elizabeth P
EP
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Malboeuf
Christine M
CM
Bernard
Matthew
M
Rose
Robert C
RC
Phipps
Richard P
RP
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D014771:Virion / Q000276:immunology*
D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D053918:Papillomavirus Vaccines; D011720:Pyrazoles; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D051546:Cyclooxygenase 2