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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
Cyclooxygenase-2 inhibition attenuates antibody responses against human papillomavirus-like particles
Elizabeth P Ryan1, Christine M Malboeuf, Matthew Bernard
1Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Abstract:
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.
Insights
Cyclooxygenase-2 (Cox-2) is vital for effective antibody responses to vaccines. Inhibiting Cox-2 may reduce vaccine efficacy, impacting immunity against infectious diseases.
Area of Science:
- Immunology
- Pharmacology
Background:
- Vaccine-induced humoral immunity is critical for infectious disease prevention.
- Emerging viral strains and poorly immunogenic vaccines necessitate optimized immune responses.
- Cyclooxygenase-2 (Cox-2) role in adaptive immunity is under investigation.
Purpose of the Study:
- To investigate the role of Cox-2 in antibody (Ab) responses to human papillomavirus type 16 virus-like particles (HPV 16 VLP) vaccination.
- To assess the impact of Cox-2 inhibition on B cell differentiation and Ab production.
Main Methods:
- Utilized Cox-2-deficient (Cox-2(-/-)) and wild-type mice for vaccination studies.
- Administered HPV 16 VLPs and measured IgG, Ab-secreting cells, and neutralizing Ab.
- Assessed B cell differentiation using SC-58125, a Cox-2 inhibitor, in human memory B cells.
Main Results:
- Cox-2(-/-) mice showed significantly reduced IgG (70% less), Ab-secreting cells (50% fewer), and neutralizing Ab (10-fold less) post-HPV 16 VLP vaccination.
- Impaired class switching contributed to the reduced Ab production in Cox-2(-/-) mice.
- SC-58125 treatment reduced human memory B cell differentiation into IgG-secreting cells by approximately 70%.
Conclusions:
- Cox-2 is essential for optimal humoral immune responses to HPV 16 VLP vaccination.
- Cox-2 inhibitors, including NSAIDs and selective inhibitors, may diminish vaccine efficacy.
- Caution is advised regarding the use of Cox-2 inhibitors around vaccination, particularly for vulnerable populations.
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