Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination

Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8⁺ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.