During the COVID-19 pandemic, mRNA vaccines were developed rapidly and saved countless lives worldwide.
Now, researchers at Boston Children’s Hospital’s Precision Vaccines Program are working on new technologies that could make these vaccines even better.
Their innovations could lead to mRNA vaccines that are more powerful, last longer, require smaller doses, and cause fewer side effects.
The current mRNA COVID-19 vaccines, like those from Pfizer/BioNTech, work by instructing our cells to produce the SARS-CoV-2 spike protein.
This helps the immune system recognize the virus and produce antibodies against it.
However, these vaccines only provide short-term protection, requiring frequent booster shots. They also work less effectively in people over 60 and can cause inflammatory side effects.
Dr. David Dowling’s lab at Boston Children’s Hospital has been looking for ways to improve these vaccines.
“Current mRNA vaccines don’t control how the immune system is activated, which can lead to unpredictable results,” says Dowling. “We wanted to design a vaccine that addresses these issues.”
One of their key innovations involves a naturally occurring immune protein called interleukin-12 (IL-12), specifically a form known as IL-12p70. IL-12p70 plays a crucial role in activating dendritic cells, which are essential for kick-starting the immune response.
These cells help activate other immune cells that fight off infections and help create long-lasting immunity.
The researchers designed a new mRNA that instructs cells to produce IL-12p70. When tested in mice, this mRNA worked alongside the Pfizer/BioNTech vaccine to boost the immune response significantly.
It not only increased the production of antibodies but also enhanced the activity of other immune cells, which are vital for protecting against the virus.
Impressively, this combination worked well even in older mice, whose immune responses were similar to those of younger adults.
The new technology also helped create longer-lasting immunity. Mice that received the combination of the IL-12p70 mRNA and the Pfizer/BioNTech vaccine showed strong immune responses even a year later.
This suggests that such a vaccine could reduce the need for frequent boosters in humans.
Another innovation from the team involves reducing the side effects of mRNA vaccines. They developed a technology called the Multi-Organ Protection (MOP) sequence, which ensures that the mRNA acts primarily in muscle cells where the vaccine is injected.
This prevents the mRNA from affecting other tissues, reducing the risk of side effects.
The researchers found that combining the IL-12p70 mRNA with the MOP sequence allowed for strong immune responses with much lower vaccine doses. This could be crucial in situations where a rapid increase in vaccine supply is needed.
“Our approach allows us to use lower doses of the vaccine while still achieving a strong immune response,” says Dr. Byron Brook, one of the study’s co-leaders. “This is a significant step toward making mRNA vaccines more widely available and effective.”
The team is now testing their innovations in primates, whose immune systems are closer to those of humans, with hopes of beginning a Phase 1 clinical trial soon.
These advancements could potentially be applied to other mRNA vaccines in development, like flu vaccines, and may represent a significant leap forward in vaccine technology.
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