Updated:05/31/2022 8:00 p.m.
People who experienced severe fatigue after vaccination were more likely to have higher baseline expression of genes related to the activity of T cells and natural killer cells. Furthermore, experiments in mice suggest that changing the injection strategy of the vaccine could alleviate these adverse effects.
Despite their great efficacy against SARS-CoV-2, mRNA-based Covid-19 vaccines are associated with adverse effects after vaccination, such as fatigue; how could this be avoided?
In a study published in “PLOS Biology,” Ayesa Syenina, of Duke-NUS Medical School in Singapore, and colleagues report that a new analysis of blood samples from people vaccinated against Covid-19 has identified molecular features different linked to a greater probability of fatigue after vaccination.
Adverse effects after vaccination may influence the provision people to get vaccinated or get a booster dose, hampering efforts to reduce the spread and severity of Covid-19. However, the molecular underpinnings of post-vaccination adverse effects are unclear.
To improve understanding, Syenina and colleagues analyzed blood samples from 175 healthcare workers who received BNT162b2, Pfizer-BioNTech’s Covid-19 vaccine. Specifically, they used the blood samples to analyze a snapshot of each participant’s gene expression—that is, which genes are turned on or off.
The researchers also tested two different vaccine injection strategies in mice. Some mice received BNT162b2 by intramuscular injection, the current method used for human patients, in which the vaccine is injected into the muscles. Other mice received an isubcutaneous Injection, in which the vaccine is injected into the tissue just below the skin.
Following vaccination, compared to mice receiving the intramuscular vaccine, mice receiving the subcutaneous vaccine showed immune system responses consistent with a less chance of side effects such as fatigue. However, subcutaneous injection did not appear to compromise the protective effects of vaccination.
Further research will be necessary to develop these findings and explore their clinical significance. Still, they increase understanding of postvaccination fatigue and offer a possible strategy to reduce its likelihood.
Eong Ooi, co-author of the study, adds: “This study provides a first glimpse of the molecular basis of a side effect that many have experienced after vaccination with mRNA. We hope that this finding will prompt further studies to fully understand the mechanisms underlying vaccine-associated side effects and collectively contribute to developing even more tolerable vaccines.”