Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection

Abstract

Despite substantial improvements, influenza vaccine production-and availability-remain suboptimal. Influenza vaccines based on mRNA may offer a solution as sequence-matched, clinical-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. Here we show that mRNA vaccines induce balanced, long-lived and protective immunity to influenza A virus infections in even very young and very old mice and that the vaccine remains protective upon thermal stress. This vaccine format elicits B and T cell-dependent protection and targets multiple antigens, including the highly conserved viral nucleoprotein, indicating its usefulness as a cross-protective vaccine. In ferrets and pigs, mRNA vaccines induce immunological correlates of protection and protective effects similar to those of a licensed influenza vaccine in pigs. Thus, mRNA vaccines could address substantial medical need in the area of influenza prophylaxis and the broader realm of anti-infective vaccinology.

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

“…Nonretroviral RNA vaccines are attractive due to their inherent transience and absence of recombination or integration into the patient's genome. However, RNA-based vaccines require intracellular delivery methods to function (24)(25)(26)(27)(28)(29).…”

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study

“…Alternatively, intentional stimulation of the native TCRs by viral vaccines may produce equal benefit, with greater predictability. 39,40 Authorship Contribution: C.R.Y.C. designed and performed the in vitro experiments, analyzed data, and wrote the manuscript; K.P.M.…”

Dendritic Cell Targets for Self-Replicating RNA Vaccines

“…Nevertheless, mRNA vaccines can be generated with applicability as "naked" RNA (no delivery vehicle). Such approaches require that the mRNA be protected from RNase degradation, for example by 5' capping and/or addition of a poly-A tail at the 3' end, or addition of protamine [20,[27][28][29][30]. An alternative to the capping strategy has employed large quantitates of the mRNA vaccines [20,31].…”

“…RNA vaccine development has found a clear level of success, with most vaccines based on the mRNA principle [8,20,27,33]. A substitute to the employment of "naked" mRNA or high concentrations, and thus circumventing their inherent restrictions, comes from the field of biodegradable delivery vehicle application.…”

“…These are often delivered as "dendritic cell vaccines" whereby the DCs have been transfected with the mRNA [8,[58][59][60][61][62][63][64], but mRNA vaccines have been employed for direct vaccination [62,64,65] and nanoparticulate delivery [59]. Such approaches were also applied in fields other than cancer vaccination [8,59], for example against HIV [58] and influenza [27]. Importantly, self-amplifying replicon RNA vaccines have been trialled as VRPs [56,[66][67][68][69], which demonstrates the high potential for these RNA vaccines when delivered by nanoparticulate vehicles to DCs.…”