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.

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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