New universal flu vaccine offers broad protection against influenza A virus infections, researchers find

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Rational design of chimeric M2e-H3 stalk protein, purification and confirmation. A schematic of the full length HA gene of the influenza A virus (A/Aichi/H3N2) and the selective domains as a vaccine target are numbered in amino acid residues (aa 37-61, 305-338, 1-117). B M2e-H3 stem vaccine construct with flexible and soluble linker sequences (AAAGGAA; GGGGS; GSA; GSAGSA; QGTGG). C The monomeric H3 HA 3D cartoon structure as predicted by the SWISS model and visualized in PyMol. D Illustration of the cartoon monomeric structure of the M2e-H3 stalk domain marking the positions of point mutations. M2e and foldon structures were modeled with PDB ID codes 4N8C and 1RFO, respectively. E Coomassie Blue staining of M2e-H3 stalk protein. Marker: marker for protein size (kDa), crude TP: total cell lysates (25 µg); M2e-H3 stem: purified M2e-H3 stem protein (15 µg). F Western blot of M2e-H3 stalk protein. 14C2: M2e-specific mAb; stem: anti-fusion peptide (FP) polyclonal antibody (pAb) that recognizes HA2 aa1-14-epitope. Credit: npj vaccines (2022). DOI: 10.1038/s41541-022-00498-6

A new universal flu vaccine, made with key components of the influenza virus, provides broad cross-protection against different strains and subtypes of influenza A viruses in young and older populations, according to a new study by researchers at Georgia State University’s Institute for Biomedical Sciences.

The researchers developed the universal flu vaccine by genetically linking two highly conserved (relatively unchanged over time) parts of the virus – the extracellular domain of matrix 2 (M2e) and the stem protein found in influenza A H3N2 viruses. The findings, published in the journal npj vaccinesshow that vaccination with M2e stalk proteins induced broad protection against various influenza virus strains and subtypes by universal vaccine-mediated immunity in adult and aged mice.

Scientists have faced obstacles in developing effective vaccines for: flu viruses because the main body of the flu virus is constantly changing. When comparing the H1N1 and H3N2 influenza A viruses, specific challenges exist in H3N2 subtypes due to stem mutations in circulating strains and the unstable structure of stem proteins for H3N2 viruses. These drawbacks have been difficult to overcome when developing effective H3-stem-based vaccines.

Vaccine effectiveness against H3N2 has been low for the past decade, only about 33 percent, falling to 6 percent during the 2014-2015 flu season. New mutations of H3N2 variants emerged with increased virulence. Also, the outbreak of H7N9, another influenza A subtype, raised concerns about potential pandemics. Therefore, the development of an effective vaccine to protect against these viruses is a high priority.

“The M2e stalk protein could be easily produced in high yield bacterial cell cultures for the first time and was found to provide protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2, and H7N9) at comparable levels in adults. and old mice,” said Dr. Sang-Moo Kang, senior author of the study and a professor at Georgia State’s Institute for Biomedical Sciences. “These results provide evidence that M2e-stalk genetic fusion proteins can be produced on a large scale at low cost and developed as a universal candidate for influenza A virus vaccine for young and elderly populations.”

The study found that this novel M2e stalk protein vaccine induced M2e and stalk specific Immunoglobulin G (IgG) antibodies that recognized antigenically different influenza virus antigens on virus particles and on the infected cell surface. In addition, the vaccine stimulated protective cellular immunity of T cells and effective lung function influenza viral clearance in mice.

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More information:
Jeeva Subbiah et al, A chimeric thermostable M2e and H3 stem-based universal influenza A virus vaccine, npj vaccines (2022). DOI: 10.1038/s41541-022-00498-6

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