Subcutaneous injection of the COVID-19 vaccines may reduce the adverse post-vaccination effects, such as fatigue, while still providing similar immune-system responses, according to a study in mice. Currently, mRNA-based COVID-19 vaccines are injected deep into the muscles, which is called intramuscular injection. An alternative type of shot is called subcutaneous injection, where a short needle can inject medication 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 on Tuesday in the journal PLOS Biology, analyzed blood samples from people vaccinated for COVID-19 and identified distinct molecular characteristics linked to an increased likelihood of post-vaccination fatigue. Experiments in mice suggest that switching the vaccine injection strategy could potentially ease such adverse effects.
“This study provides the first insight into the molecular basis of a side effect that many have experienced following mRNA vaccination,” said study coauthor Eng Eong Ooi from the Duke-NUS Medical School in Singapore.“We hope that this finding would spur more studies to fully understand the underpinning mechanisms behind vaccine-associated side effects and collectively contribute to developing even more tolerable vaccines,” Ooi said in a statement.
Adverse post-vaccination effects may influence people's willingness to get vaccinated or receive a booster dose, hampering efforts to reduce the spread and severity of COVID-19, the researchers said. However, the molecular underpinnings of adverse post-vaccination effects have been unclear, they said. To improve understanding, the researchers analyzed blood samples from 175 healthcare workers who received the Pfizer-BioNTech COVID-19 vaccine. They used the blood samples to analyze a snapshot of each participant's gene expression, or which genes are turned on or off. The analysis shows that people 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 key cell types in the human immune system.
The researchers also tested two different vaccination injection strategies in mice. Some mice received the vaccine through intramuscular injection, the current method used for human patients, in which the vaccine is injected into the muscles. Other mice received a subcutaneous injection, in which the vaccine is injected into the tissue just under the skin. Compared to mice that received intramuscular vaccination, those receiving subcutaneous vaccine showed immune-system responses that are in line with a lower likelihood of adverse effects such as fatigue. However, the subcutaneous injection did not appear to compromise the protective effects of vaccination, the researchers added.
