Glycan adjuvantation expands the breadth and duration of protection of a mRNA-based vaccine

Inflammation initiated in response to microbial encounter, or deliberately induced upon vaccination, is central for the activation of adaptive lymphocytes. The stimulation of pattern recognition receptors (PRRs) orchestrates the inflammatory programs that regulate adaptive immunity. Nevertheless, only few PRRs have been tested for their capacity to potentiate the efficacy of vaccines. Here, we took advantage of a mRNA-based vaccine generated against the ancestral Spike protein of SARS-CoV-2 to test whether tuning inflammation enhances the efficacy of the vaccine. We combined a mRNA-based vaccine with the mannadjuvant, a formulation of fungal mannan and alum hydroxide that targets a class of PRRs known as C-type lectin receptors. The mannadjuvant increased the magnitude and durability of the response elicited by the mRNA-based vaccine, and it also led to the induction of neutralizing antibodies directed against variants of concern with a high escape capacity. Overall, our data demonstrate that inflammation can be harnessed to create more potent and durable mRNA-based vaccines.