A bivalent self-amplifying RNA vaccine against yellow fever and Zika viruses

Monovalent vaccines established durable neutralizing antibody responses to their respective flaviviral targets, with little evidence of cross-neutralization. Both vaccines additionally elicited robust antigen-reactive CD4⁺ and CD8⁺ T cell populations. Notably, humoral responses to YFV saRNA-NLC vaccination were comparable to those in YF-17D-vaccinated animals. Bivalent formulations established humoral and cellular responses against both viral targets, commensurate to those established by monovalent vaccines, without evidence of saRNA interference or immune competition. Finally, both monovalent and bivalent vaccines completely protected mice and hamsters against lethal ZIKV and YFV challenge. We present a bivalent saRNA-NLC vaccine against YFV and ZIKV capable of inducing robust and efficacious neutralizing antibody and cellular immune responses against both viruses. These data support the development of other multivalent saRNA-based vaccines against infectious diseases.