Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

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.

Vaccination of Poultry Against Influenza

“…DNA vaccines deliver a foreign antigen through inoculation of the host with plasmid DNA encoding the IAV antigen, which will then be produced in the host (37). The first DNA vaccine studied in poultry in 1993 was directed against IAV (38, 39) and the strategy continues to be widely studied in chickens (37). Despite early promise, DNA vaccines induced limited immune responses and/or protection and none have become commercially available.…”

Promising strategy for developing mRNA-based universal influenza virus vaccine for human population, poultry, and pigs– focus on the bigger picture

“…Influenza viruses are negative-sense segmented RNA-containing viruses. IAV and IBV cannot be distinguished virtually and their genome comprises eight segments of RNA, each is responsible for encoding two different glycoproteins– hemagglutinin (HA) and neuraminidase (NA) that are protruded on the viral surface and play a major role in viral entry and egress, respectively ( 30 , 31 ); matrix (M2) ion channel protein which enables the proton transport and balances pH across the viral envelope during the entry into the host cell and exit ( 32 ); matrix (M1) protein which makes the scaffold beneath the virus membrane and helps the virus in the trafficking of the genome segments in the cell ( 33 , 34 ); RNA-dependent RNA polymerase complex encompassing one “polymerase acidic” (PA) and two “polymerase basic” (PB1 and PB2) subunits; nucleoprotein (NP) that coats the viral RNA segments ( 4 , 7 ); nuclear export protein (NEP) which regulates the transport of viral ribonucleoproteins from the nucleus and allows packaging of progeny virions ( 7 ). Importantly, the classification of IAVs into subtypes comes from their structure ( 35 ).…”

“…The names of pandemic influenza strains are generated according to the species where this genomic rearrangement takes place. This is the reason why the pandemic H1N1 was called swine flu in 2009– the pig played the role of mixing vessel for swine, human, and avian viruses ( 4 , 12 , 41 , 44 ). On the other hand, except for the important role of the pigs in the adaptation of IAVs to humans and other mammals, their infection itself causes a huge economic loss in pig production worldwide ( 45 ).…”

“…Indeed, as a zoonotic respiratory disease, influenza has great pandemic potential and poses the threat to humans as well as animals ( 3 ) which ultimately increases the reassortment risk of genome segments, transmissibility to humans, and facilitates the emergence of new pandemics. There are four types of antigenically distinct influenza viruses (A, B, C, and D) ( 4 ) out of which two types are regarded as health threats. Particularly, influenza A and B are the cause of seasonal epidemics while A provokes pandemics.…”

The potential benefits of delaying seasonal flu vaccine selections: a retrospective modeling study

“…engineers a vector virus so that it expresses the antigenic proteins in vector virus-infected insects or plants can produce large amounts of flu vaccines in 5-8 weeks (18). Since COVID-19 pandemic, mRNA vaccines start to expand to other respiratory diseases including seasonal flu, with their capability to deliver antigenic proteins without replicating virus in cells or eggs (19,20).…”