The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

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.

Preparing for the Coronavirus Disease (COVID-19) Vaccination: Evidence, Plans, and Implications

“…However, there is no recommendation to date, and some studies suggest that the use of antipyretic analgesics prior to vaccination may alter the immune response. 52 53 Therefore, no special premedication is required.…”

Protection Elicited by Attenuated Live Yersinia pestis Vaccine Strains against Lethal Infection with Virulent Y. pestis

“…Nevertheless, there is ample evidence that CMI contributes to vaccine responses to Y. pestis ; CMI should continue to be evaluated in ongoing tests of vaccine efficacy against a larger range of Y. pestis strains and variants, such as strain C12. T-cell derived cytokines (especially TNF-α and IFN-γ) are reported to induce the antimicrobial functions of macrophages, such as reactive oxygen and nitrogen intermediates, and help them to combat infection by facultative intracellular pathogens such as Y. pestis [ 21 , 24 , 25 , 26 , 129 , 130 ]. Moreover, it is thought that antibodies and cellular responses both contribute to protection against plague independently; it was shown that cytokine responses (i.e., TNF-α and IFN-γ) conferred significant protection, even in the absence of a protective antibody [ 23 , 25 , 26 ].…”

Plague Prevention and Therapy: Perspectives on Current and Future Strategies

“…Bubeck and Dube achieved significant protection when using a ∆yopH live vaccine strain [136] and Bozue et al, demonstrated that a Y. pestis ∆yscN mutant strain also offered significant protection against challenge with a fully virulent strain of Y. pestis [134,137]. Follow-on studies further characterized the vaccine potential of ∆yscN strains of Y. pestis as well as a strain lacking both the pigmentation (pgm) locus and the pPst virulence plasmid [138][139][140][141]. In addition, promising results were obtained with Y. pseudotuberculosis based live vaccines that conferred protection and immunological memory [142][143][144][145].…”