A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes

A universal flu vaccine on the way?

Because we cannot currently predict which subtype of the influenza virus will cause the next pandemic, researchers have made various attempts to produce a “universal” vaccine that could protect people from a wide swathe of subtypes. Although most of these efforts have focused on a limited set of antigens that are shared by many subtypes, an alternate approach has been to generate a multivalent vaccine that would encode all known subtypes. Arevalo et al. took advantage of recent advances in nucleic acid–based vaccine platforms to develop a nucleoside-modified messenger RNA–lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A and B virus subtypes (see the Perspective by Kelvin and Falzarano). This vaccine elicited high levels of cross-reactive and subtype-specific antibodies in both mice and ferrets, which protected these animals from matched and mismatched influenza virus strains. —STS

Abstract

Seasonal influenza vaccines offer little protection against pandemic influenza virus strains. It is difficult to create effective prepandemic vaccines because it is uncertain which influenza virus subtype will cause the next pandemic. In this work, we developed a nucleoside-modified messenger RNA (mRNA)–lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A virus subtypes and influenza B virus lineages. This multivalent vaccine elicited high levels of cross-reactive and subtype-specific antibodies in mice and ferrets that reacted to all 20 encoded antigens. Vaccination protected mice and ferrets challenged with matched and mismatched viral strains, and this protection was at least partially dependent on antibodies. Our studies indicate that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens.

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References and Notes

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