Self-replicating RNA vaccines delivered by viral replicon particles (VRPs) induce strong immunity, but repeated dosing on short intervals may be limited by vector responses. In patient samples and mice, VRP-srRNA vaccination generated VRP-neutralizing antibodies and T-cell responses to replicase. In mice, a third dose at two-week intervals minimally boosted transgene immunity, and prior VRP exposure reduced responses to a different-transgene VRP. Optimized schedules or heterologous prime–boost may sustain immunogenicity.
Ma et al. (Mon,) studied this question.