With input from Dr Monica Vasudev
Vaccine Reactogenicity (Part 1)
This refers to the physical manifestation of the inflammatory response to vaccination. It may include pain at the injection site, redness, swelling or induration at the injection site, and systemic symptoms, such as fever, myalgia, or headache.
Immunogenicity refers to the potential to induce a humoral and/or cell mediated immune response. Reactogenicity is the property of a vaccine to produce excessive immunological responses as well as associated signs and symptoms.
Immunogenicity and reactogenicity are sustained by inflammatory reactions (innate immunity). The difference is usually at the level of inflammatory reactions involved in both cases. A particular level of inflammatory reactions is required to sustain a good adaptive immune response. Excessive inflammatory reactions, on the contrary, impair the same adaptive immune response by causing serious inflammatory and/or oxidative conditions in certain cases.
Causes of reactogenicity
- Vaccines contain antigens that have the potential to induce an immune response which can yield specific protection from disease.
- Individual vaccine antigens induce innate immune responses that may be different qualitatively or quantitatively based on the vaccine’s composition, but induce a good adaptive immune response.
- Once they enter the body, the vaccine antigens are recognized as potential pathogens by conserved pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), pattern-recognition receptors (PRRs), including toll-like receptors (TLR), found on local or peripheral circulating immune cells (e.g. monocytes and macrophages) and on resident stromal cells.
- The transcription of several target genes is induced in these cells, in which leads to the synthesis and release of pyrogenic cytokines (interleukin [IL]-1, IL-6, tumor necrosis factor-alpha [TNF-α], and prostaglandin-E2) in the bloodstream, mimicking the response to natural infection.
- Once it is stimulated, the immune system incites a complex series of innate immune events that can include phagocytosis, inflammatory mediators release, including chemokines and cytokines, complement activation, as well as cellular recruitment.
- This is essential to trigger strong antigen-specific acquired immune responses which are required for protection against disease.
- These same inflammatory events may result in signs and symptoms of injection-site inflammation (pain, redness and swelling) in the individual who has received the vaccine.
- Mediators and products of inflammation in the circulation can impact other body systems, leading to systemic side-effects, including fever, fatigue, and headache.
- A balance between the beneficial and the detrimental effects of these inflammatory events is vital to keep reactogenicity at clinically acceptable levels.[Source: NPJ Vaccines. 2019 Sep 24;4:39; Allergy Bioinformatics. 2015; 8: 175–186.]
Dr KK Aggarwal
President CMAAO, HCFI and Past National President IMA