With input from Dr Monica Vasudev

Vaccine Reactogenicity (Part 2)

Can prophylactic medicines prevent symptoms?

1. A meta-analysis revealed that prophylactic antipyretic drugs led to a significant reduction in injection-site and systemic symptoms following vaccination. However, the use of these drugs was associated with reduced antibody responses to most vaccine antigens.
2. A review suggested that the timing of antipyretic administration was vital, as there was no effect on the antibody response if the antipyretics were given as a treatment for symptoms after vaccination, rather than for the prevention of symptoms.
3. In order to balance reactogenicity with the potential effect of prophylactic paracetamol on immunogenicity, there are only few vaccines for which prophylactic paracetamol use to prevent symptoms is actively recommended, usually in settings where different pyrogenic vaccines are co-administered, which leads to an additive effect on the incidence of fever.

Regardless of the composition, vaccines induce some level of inflammation at the injection site within the first hours following administration, likely contributing to pain, redness and swelling.

As pyrogenic factors are released into the systemic circulation, a cascade of immune and nervous system cross-talk is set off, resulting in systemic ‘influenza-like’ symptoms, including raised body temperature.

There are general associations between systemic inflammatory mediators and systemic symptoms following vaccination. However, no single biomarker of systemic reactogenicity has been identified; rather a composite of biomarkers is involved. In particular, IL-6, CRP, and for highly immunogenic products, the IFN-signaling pathway, seem to be associated with systemic reactogenicity.

It is unclear if the specific molecular pathways leading to symptoms are independent from the pathways that have a role in antigen-specific response.

Older individuals tend to exhibit lower systemic levels of IL-6, IL-10 and CRP following vaccination, which could potentially have a role in their tendency to demonstrate fewer systemic adverse events, especially fever.[Source: NPJ Vaccines. 2019 Sep 24;4:39]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA