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Review
. 2022 Apr 30;10(5):709.
doi: 10.3390/vaccines10050709.

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

Andrei A Deviatkin  1   2 , Ruslan A Simonov  2 , Kseniya A Trutneva  1   2 , Anna A Maznina  2 , Elena M Khavina  2 , Pavel Y Volchkov  1   2
Affiliations
Review

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

Andrei A Deviatkin et al. Vaccines (Basel). .

Abstract

The seasonal flu vaccine is, essentially, the only known way to prevent influenza epidemics. However, this approach has limited efficacy due to the high diversity of influenza viruses. Several techniques could potentially overcome this obstacle. A recent first-in-human study of a chimeric hemagglutinin-based universal influenza virus vaccine demonstrated promising results. The coronavirus pandemic triggered the development of fundamentally new vaccine platforms that have demonstrated their effectiveness in humans. Currently, there are around a dozen messenger RNA and self-amplifying RNA flu vaccines in clinical or preclinical trials. However, the applicability of novel approaches for a universal influenza vaccine creation remains unclear. The current review aims to cover the current state of this problem and to suggest future directions for RNA-based flu vaccine development.

Keywords: circRNA; influenza virus; mRNA vaccine; universal flu vaccine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of the influenza virus. Figure was created using BioRender tool.
Figure 2
Figure 2
Upper panel: Unrooted maximum likelihood tree for IAVs (HA gene fragment, n = 1003). Red color indicates viruses collected from swine, green from ducks, blue from chickens, yellow from ruddy turnstones. Phylogenetic inference was performed using IQ-TREE [7]. Lower panel: pairwise genetic distances for IAVs collected from swine, ducks, chickens, and ruddy turnstones.
Figure 3
Figure 3
The dynamics of the publications number with keywords “mRNA INFLUENZA VACCINE” or “live attenuated INFLUENZA VACCINE” or “inactivated INFLUENZA VACCINE” or “adenovirus INFLUENZA VACCINE” or “peptide INFLUENZA VACCINE” or “recombinant HA INFLUENZA VACCINE”.
Figure 4
Figure 4
mRNA vaccines’ method of action [40]. Five-prime cap (black circle) and polyA tail present on all mRNAs. (A), conventional mRNA encodes protein that may be used as an antigen.Apart from the gene of interest, self-amplifying mRNA (SAM) may encode RNA dependent RNA polymerase (RDRP) at the same molecule (B) or at the other mRNA (C). (B,C), step 1, translation of RDRP and gene of interest. Step 2, RDRP amplifies mRNA. Step 3, translation of self-amplified mRNA. Figure was created using BioRender tool.
Figure 5
Figure 5
Circular mRNA generation via backsplicing. Modified from [59]. Figure was created using BioRender tool.
Figure 6
Figure 6
CircRNA protection from exonuclease action. (A) Linear mRNA can be degraded by 5’ RNAse and 3’ RNAse. (B) Circular mRNA cannot be degraded by 5’ RNAse and 3’ RNAse. Figure was created using BioRender tool.
Figure 7
Figure 7
Administration routes of mRNA vaccines. Figure was created using BioRender tool.
See this image and copyright information in PMC

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