According to a study in mice, subcutaneous injection of COVID-19 vaccines can reduce post-vaccination adverse effects, such as fatigue, while still providing similar immune-system responses. Currently, mRNA-based COVID-19 vaccines are injected deep into the muscle, called intramuscular injection.
An alternative type of shot is called a subcutaneous injection, where a small needle can inject medicine into the tissue between the skin and the muscle. Despite their high efficacy against SARS-CoV-2, mRNA-based COVID-19 vaccines are associated with adverse post-vaccination effects, such as fatigue, the researchers said.
The study, published Tuesday in the journal PLOS Biology, analyzed blood samples from people vaccinated with COVID-19 and identified specific molecular features associated with an increased likelihood of fatigue after vaccination. Experiments in rats suggest that such adverse effects can be reduced by changing the vaccine injection strategy.
Study co-author Ing Eong Oi, from Duke-NUS Medical School in Singapore, said the study provides the first insight into the molecular basis of a side effect that many people experience after mRNA vaccination. “We hope this discovery will prompt more studies to fully understand the mechanisms behind vaccine-associated side effects and collectively contribute to the development of even more tolerable vaccines,” Oi said in a statement.
Post-vaccination adverse effects may affect people’s willingness to receive vaccinations or booster doses, hindering efforts to reduce the spread and severity of COVID-19, the researchers said. However, the molecular basis of the post-vaccination adverse effects remains unclear, he said.
To improve understanding, researchers analyzed blood samples from 175 healthcare workers who received the Pfizer-BioNTech COVID-19 vaccine. They used blood samples to analyze snapshots of each participant’s gene expression, or which genes are on or off. The analysis shows that those who experienced moderately 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 — two major cell types in the human immune system. The researchers also tested two different vaccination injection strategies in mice.
Some mice receive the vaccine via intramuscular injection, the current method used for human patients, in which the vaccine is injected into the muscle. Other mice received a subcutaneous injection, in which the vaccine is injected into the tissue just under the skin.
Compared with mice that received intramuscular vaccination, those receiving the subcutaneous vaccine showed immune-system responses that are consistent with a reduced likelihood of adverse effects such as fatigue. However, subcutaneous injection did not appear to compromise the protective effects of vaccination, the researchers said.
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