Novel RNA adjuvant for intradermal influenza and COVID-19 vaccine

Abstract

Vaccines are a powerful weapon to protect humans from infectious diseases, especially in the recent fight to end the coronavirus disease of 2019 (COVID-19) pandemic. Vaccine efficacy is far from satisfactory in immunocompromised populations and the elderly, both of whom are most susceptible to infectious diseases. Adding adjuvants to vaccines is a highly cost-effective strategy for improving vaccine efficacy.

In this thesis, we first established a mouse model with optimal virus inoculum and vaccine dosage to screen intradermal adjuvants. Next, we determined whether the combination of TLR7 and TLR9 agonists has superior adjuvant efficacy than TLR7 agonists alone or TLR9 agonists alone. TLR7 and TLR9 were selected because both of them are key pattern recognition receptors (PRRs) involved in innate immune responses, particularly in the detection of viruses. Finally, we found a novel RNA adjuvant, R266, an RNA derived from the 5’ untranslated region of the SARS-CoV-2 genomic sequence. R266 can improve the survival rate of mice infected with a lethal dose of influenza virus even when only one-sixth of the dose of previous influenza vaccines was immunized. We demonstrated the mechanism of R266 from the B-cell response and T-cell response of mice and found that a powerful T-cell response in the early stages of infection might be one key factor in increasing vaccine protection. We also explored the mechanism of R266 in human cell lines, and the results showed that the TLR9 pathway and Dectin-1 pathway may be its mechanism of action.

In conclusion, we demonstrated that R266 could be used as a promising intradermal adjuvant to enhance the effectiveness of the influenza vaccine. Further detailed mechanisms of R266 are worth exploring, which will lay the foundation for future innovations in RNA adjuvants and vaccines.