Blood test study may help improve performance and reduce side effects of mRNA vaccines

A study by researchers at RMIT University and the Doherty Institute has provided the first detailed analysis of how mRNA vaccines circulate and break down in human blood. The research aimed to help improve the safety and effectiveness of these vaccines, including reducing common side effects such as headache, fever and fatigue.

Since the introduction of the first mRNA COVID-19 vaccines, scientists have harnessed the technology to develop vaccines and treatments for a variety of other diseases, including cancer.

These mRNA vaccines use genetic instructions, instead of a weakened virus, to trigger the body to produce a protein that triggers an immune response. Their rapid development, adaptability to new variants and strong safety profile have made them essential in the global fight against the COVID-19 pandemic.

The study, “Blood distribution of SARS-CoV-2 lipid nanoparticle mRNA vaccine in humans,” published in ACS Nanoanalyzed 156 blood samples from 19 people over 28 days after receiving a Moderna SPIKEVAX mRNA booster. The team discovered key insights into the movement and breakdown of vaccine components in the bloodstream, critical to developing safer and more effective vaccines.

Dr Yi (David) Ju, an Australian Research Council DECRA Fellow at RMIT University, is co-lead author of the study with Professor Stephen Kent of the University of Melbourne, Laboratory Head at the Doherty Institute .

Reducing the side effects of mRNA vaccines

These vaccines are designed to stay in lymph nodes to produce antibodies to fight infections, but researchers say a tiny amount of the vaccine also ended up in the bloodstream.

“The extent to which the vaccine enters the bloodstream varies among individuals, which may explain some of the side effects, such as fever, headache and fatigue, reported after vaccination,” Ju said. School of Science.

“This variation in the presence of the vaccine in the blood could trigger inflammatory responses, leading to these side effects in some individuals. Understanding the causal relationship between the amount of vaccine circulating in the blood and these side effects will be an important area for future research.

“To be clear, the amounts of vaccine entering the bloodstream are very small, allowing people to be confident that mRNA vaccines are safe and effective.”

How long does the mRNA vaccine that reaches the bloodstream stay there?

The study revealed how mRNA and its shell of fatty nanoparticles peaked in the bloodstream two days after vaccination. In some cases, mRNA remains detectable for up to a month.

Researchers initially predicted that it is the antibodies formed in response to a commonly used vaccine compound, known as polyethylene glycol (PEG), that determine how long a vaccine stays in the blood. However, the research team found that anti-PEG antibodies were not the only factor impacting this process.

Ju said mRNA breakdown in the body was also likely influenced by a complex mix of individual factors.

“The mRNA vaccine in the blood is like a message in a bottle. It is protected by its shell – the fatty nanoparticles – as it travels, but its fate depends on how the body reacts to the bottle, not just the message that ‘it contains,’ Ju said. said.

“However, we found that higher levels of mRNA and fat nanoparticles in the blood were linked to a greater increase in anti-PEG antibodies, suggesting that some individuals may develop more anti-PEG antibodies. “

Developing safer and more effective mRNA vaccines

Kent said that if people developed high levels of anti-PEG antibodies from the mRNA vaccines, it could reduce the effectiveness of future mRNA treatments for diseases such as cancer, because their bodies would eliminate more treatments. quickly.

“By understanding the biodistribution of these components, we can better inform future vaccine designs to minimize risks. Our study offers valuable insights into improving mRNA vaccines for safer and more effective use,” said Kent.

Researchers could use this information to optimize fatty nanoparticle formulations to improve mRNA stability, which could lead to a prolonged immune response and reduce the likelihood of rapid clearance from the body. Further research could also help find a way to prevent vaccines from entering the bloodstream.

“By identifying individual factors that affect mRNA circulation, future vaccines can be tailored to personal characteristics, thereby improving effectiveness on a case-by-case basis,” Ju said.