Adjuvants to Prevent Against Waning Immunity in mRNA Vaccines

All vaccines are known to have some level of waning immunity. The extent to which vaccine efficacy decreases is impacted by many factors, such as the characteristics of the infectious agent and the type of vaccine (https://pmc.ncbi.nlm.nih.gov/articles/PMC9015327/).

When mRNA vaccines for COVID-19 began to hit the market, people became concerned that these vaccines weren’t durable and immunity would wane after 4 to 6 months, prompting even more regular boosters. Scientists have debunked this claim and shown that some mRNA vaccines are good at preventing severe disease in up to 97% of patients after 9 to 12 months (Bansal et al. Duration of COVID-19 mRNA Vaccine Effectiveness against Severe Disease. Vaccines (Basel). 2022 Jun 28;10(7):1036. doi: 10.3390/vaccines10071036. PMID: 35891199; PMCID: PMC9321581.).

Combined Therapeutics aims to improve this duration even further with the use of mRNA encoding for cytokines that can be used as adjuvants.

Utilizing cytokines, like IL-12, as an adjuvant isn’t a novel innovation, but encoding an mRNA for a cytokine and formulating it with a standard mRNA vaccine is a new approach that has shown increased potential to boost efficacy and durability. IL-12 is known to increase the function of naïve B cells and assist in the process of developing memory B cells needed for long term immunity. By dosing Pfizer/BioNTech’s vaccine with mRNA encoding for IL-12, CTx was able to see minimal decreases in anti-Spike antibodies after 1 year in mice as compared to the vaccine alone. This shows the promise of CTx’s adjuvant portfolio to improve durability of mRNA vaccines, which could be beneficial for countries with less health care infrastructure by reducing the need for regular boosters.