Manage the discomfort following vaccination: would painkillers weaken the immune response?
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As mentioned in my earlier article “A Brief History of Vaccines: an endless war between humans and pathogens”, vaccination is an effective preventive measure against many infectious diseases at both individual and population levels. But the side effects are a major reason that some people are hesitant to receive a vaccine. Common side effects associated with a vaccine include pain at the injection site, headache, myalgia, fever, and fatigue, and they can last for a few days. To manage the discomfort caused by a vaccine, out-the-counter pain relievers such as acetaminophen in Tylenol, Aspirin in Ecotrin, and ibuprofen in Advil are the common options. But some may worry these drugs would weaken the immunity provided by the vaccine, as these drugs suppress the immune pathway that is crucial for activating the immune reaction. Several clinical studies have shown that the impact of pain relievers on vaccine efficacy is limited, but some vaccines are more likely to be affected than others. The antibody responses to certain vaccines such as PHiD-CV (pneumococcal) and combined vaccine DTPa-HBV-IPV/Hib (diphtheria, tetanus, pertussis, hepatitis B, poliovirus, and H influenzae type b) may be affected by acetaminophen and ibuprofen during childhood, whereas these drugs don’t seem to affect the antibody titers in adults. Despite blunted antibody titers to certain vaccines, by far there is no clinical evidence showing that over-the-counter pain relievers would impact the protective effects of vaccines.
As in most cases the side effects are self-resolved, the causes of vaccine side effects have received little attention from researchers. However, based on the observation of how actual pathogens cause symptoms, the production of immune signaling molecules known as cytokines is likely the cause of vaccine-associated side effects. Immune cells like macrophages and dendritic cells function as the sentinels watching out for pathogens, they detect the existence of pathogens by recognizing their specific molecular fingerprint known as pathogen-associated molecular patterns (PAMAs). Upon sensing pathogens via their PAMAs in the tissue, macrophages and dendritic cells release cytokines named type-I interferon (IFN-I) to initiate the early immune response against the pathogen. Such a response is crucial for producing optimal immune responses including T cells and antibodies. Therefore, most vaccines are designed to trigger such reactions. However, the release of INF-I usually can cause symptoms like fever, headaches, and fatigue — the typical side effects of vaccination.
Schematic of how COVID-19 mRNA vaccine may trigger the release of type-I interferon (IFN-I) and activate humoral (antibody) and cellular immunities. Image from Science Immunology by Jonathan Sprentm et al.
Common nonsteroid anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin reduce pain and inflammation by suppressing inflammatory pathways involving prostaglandin synthesis and cyclo-oxygenase 1 and 2 (COX-1 and COX-2) activities. Acetaminophen, classified as an analgesic and antipyretic not an NSAID, has been widely used, but its mechanism of action remains unclear. It may exert its therapeutic effects via inhibiting COX-1 and COX-2 too, but other mechanisms have also been suggested. As both COX-2 and prostaglandin are important in the immune response signaling mentioned earlier, the use of these types of pain relievers may, in theory, suppress the immune responses induced by a vaccine.
However, clinical studies show that acetaminophen, ibuprofen, aspirin, and indomethacin have no observed impact on antibodies induced by vaccines in adults, while some limited effect on certain vaccines was reported with acetaminophen and ibuprofen in children. In a non-inferiority study by Falup-Pecurariu et al., acetaminophen was given to infants immediately or several hours after the first and second doses of PHiD-CV and DTaP-HBV-IPV/Hib vaccines. Compared to those who did not receive acetaminophen, infants who received acetaminophen seemed to have lower antibody titers to the vaccines. Yet, the difference was not statistically significant, meaning we cannot rule out the possibility that this reduction in antibody titers was due to a random effect not because of acetaminophen. In another study by Wysocki et al., where infants were treated with acetaminophen or ibuprofen after receiving the 13-valent pneumococcal (PCV13) and DTaP-HBV-IPV/Hib vaccines, antibody titers were found weaker to 5 out of the 13 pneumococcal strains in infants treated with acetaminophen after the first dose. No difference in antibody titer was observed after the second dose. Ibuprofen did not seem to have the same effect on the pneumococcal vaccine, but the response to pertussis and tetanus was weaker in the ibuprofen-treated group after the first dose of vaccines.
Summary of several clinical studies using different over-the-counter pain relievers to manage discomfort following vaccination in children and adults. Table was adopted and modified from npj Vaccines by Eng Eong Ooi et al., the link to each study shown in the table can be found in this paper.
Over-the-counter pain relievers can reduce the antibody response to certain vaccines in children, but they don’t seem to affect the vaccine-induced antibody response in adults. This result suggests the effects of these drugs may vary for different age groups and vaccines. So, a more comprehensive study, where different vaccines, age groups, and pain relievers are included, is needed to answer whether a given pain reliever would affect vaccine efficacy.
Please know that the result from the mentioned clinical studies in this article may or may not apply to your medical condition. Consult your personal healthcare provider for the use of over-the-counter pain relievers to manage discomfort caused by vaccination.
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