Researchers at Boston Children's Hospital have developed two novel technologies aimed at enhancing mRNA vaccines, making them more effective and longer-lasting.

One of the key focuses of the study, published in Science Translational Medicine, is optimizing immune responses using interleukin-12 (IL-12), particularly a form called IL-12p70.

When tested on mice, the new mRNA acted as an adjuvant to the BioNTech/Pfizer vaccine, significantly boosting immune responses and producing long-lasting immunity.

Self-amplifying mRNA constructs can enhance immune responses while using a lower dose of the vaccine.

Another innovative technology introduced is a Multi-Organ Protection (MOP) sequence that ensures mRNA distribution is controlled, targeting only muscle cells to reduce side effects.

This MOP sequence allows the vaccine to act primarily on muscle tissue while recycling the mRNA in other vital organs, preventing unwanted immune responses.

Current mRNA COVID-19 vaccines provide short-lived immunity and require frequent boosters, especially for individuals over 60, and can cause significant side effects.

Incorporation of modified nucleotides, such as pseudouridines, into mRNA can enhance stability and reduce immunogenicity.

Studies indicate that both the structure and chemical composition of mRNA and its delivery systems significantly affect the induction of immune responses.

Lipid nanoparticles (LNPs) are crucial for mRNA delivery, enhancing transfection efficiency and reducing immune reactions.

The composition of LNPs can influence the activation of pattern recognition receptors (PRRs) and subsequent cytokine production.

The research team is currently testing their technologies in primates, with plans to advance to a Phase 1 clinical trial, aiming to adapt the method for other mRNA vaccines like flu vaccines.