Abstract

The administration of antipyretic analgesics prior to, in conjunction with, or due to sequelae associated with vaccination is a common yet somewhat controversial practice. In the context of human vaccination, it is unclear if even short-term analgesic regimens can significantly alter the resulting immune response, as literature exists to support several scenarios including substantial immune interference. In this report, we used a live attenuated Yersinia pestis vaccine to examine the impact of analgesic administration on the immune response elicited by a single dose of a live bacterial vaccine in mice. Mice were assessed by evaluating natural and provoked behavior, as well as food and water consumption. The resulting immune responses were assessed by determining antibody titers against multiple antigens and assaying cellular responses in stimulated splenocytes collected from vaccinated animals. We observed no substantial benefit to the mice associated with the analgesic administration. Splenocytes from both C57BL/6 and BALB/c vaccinated mice receiving acetaminophen have a significantly reduced interferon-gamma (IFN-γ) recall response. Additionally, there is a significantly lower immunoglobulin (Ig)G2a/IgG1 ratio in vaccinated BALB/c mice treated with either acetaminophen or meloxicam and a significantly lower IgG2c/IgG1 ratio in vaccinated C57BL/6 mice treated with acetaminophen. Taken together, our data indicate that the use of analgesics, while possibly ethically warranted, may hinder the accurate characterization and evaluation of novel vaccine strategies with little to no appreciable benefits to the vaccinated mice.

Highlights

  • The administration of antipyretic analgesics is a routine practice for patients receiving vaccinations and is recommended to ameliorate local and systemic side effects like fever and pain [1,2].Vaccines 2019, 7, 205; doi:10.3390/vaccines7040205 www.mdpi.com/journal/vaccinesAnalgesics such as acetaminophen, meloxicam, or ibuprofen are used as preventive strategies to reduce vaccine-related reactogenicity initiated at the time of vaccine administration and/or post-vaccination [2].Adverse vaccination reactions such as localized swelling, rash, pain, and systemic reactions of fever, muscle pain, vomiting or diarrhea, and in severe cases central nervous system effects may entice some patients to use analgesics with or without medical directives in conjunction with vaccinations.These reactions usually occur within 24–48 h following the vaccination

  • Results showed that fever was significantly reduced in children that were given analgesic, but antibody titers were significantly lower when compared with children that did not receive analgesia

  • We evaluated the immune response elicited by a live attenuated Yersinia pestis vaccine when the analgesics acetaminophen or meloxicam were given to BALB/c or C57BL/6 mice

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Summary

Introduction

The administration of antipyretic analgesics is a routine practice for patients receiving vaccinations and is recommended to ameliorate local and systemic side effects like fever and pain [1,2].Vaccines 2019, 7, 205; doi:10.3390/vaccines7040205 www.mdpi.com/journal/vaccinesAnalgesics such as acetaminophen, meloxicam, or ibuprofen are used as preventive strategies to reduce vaccine-related reactogenicity initiated at the time of vaccine administration and/or post-vaccination [2].Adverse vaccination reactions such as localized swelling, rash, pain, and systemic reactions of fever, muscle pain, vomiting or diarrhea, and in severe cases central nervous system effects may entice some patients to use analgesics with or without medical directives in conjunction with vaccinations.These reactions usually occur within 24–48 h following the vaccination. Analgesics such as acetaminophen, meloxicam, or ibuprofen are used as preventive strategies to reduce vaccine-related reactogenicity initiated at the time of vaccine administration and/or post-vaccination [2]. Adverse vaccination reactions such as localized swelling, rash, pain, and systemic reactions of fever, muscle pain, vomiting or diarrhea, and in severe cases central nervous system effects may entice some patients to use analgesics with or without medical directives in conjunction with vaccinations. A follow-up study in 2013 by Prymula et al evaluated the effect of acetaminophen on the long-term persistence and boosting of antibody in response to a multi-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine [5]. The immune blunting that was observed in the initial study was not observed after a booster vaccination, suggesting that antipyretic analgesics may not affect memory B cells

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