A Synthetic Virology Platform for Rapid Prototyping of Influenza A Virus mutants

Abstract

Influenza A virus (IAV) remains a significant public health threat, with the need for effective vaccines and antiviral therapies remaining a high priority. In vitro testing is paramount in studying novel IAV viruses and their immunogenicity. To address this need, we developed a synthetic virology approach to rapidly prototype and test IAV mutants with altered antigenic sites. By strategically inserting restriction sites within an ambisense plasmid, we generated a tool where we can seamlessly replace either 1) the full hemagglutinin (HA), 2) the HA globular head domain to generate head/stalk chimeras or 3) the five canonical antigenic sites. The cloning inserts can be computationally designed and artificially synthesized, enabling rescue of synthetic Influenza A viruses. Using this platform we rescued IAV H1N1, H3N2 & H5N1, and went on to prototype their respective antigenic site mutants & chimeric IAVs using viral genome sequence alone. This platform could be useful for generating vaccine seed strains or to study anti-viral immunity.

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BibTeX RIS

BibTeX

@misc{murti2026synthetic,
  title = {{A Synthetic Virology Platform for Rapid Prototyping of Influenza A Virus mutants}},
  author = {J. R. Murti and K. Schön and D. Angeletti},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.24.761556},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761556v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - A Synthetic Virology Platform for Rapid Prototyping of Influenza A Virus mutants
AU  - J. R. Murti
AU  - K. Schön
AU  - D. Angeletti
PY  - 2026
DA  - 2026/10/24
PB  - bioRxiv
DO  - 10.64898/2026.10.24.761556
UR  - https://www.biorxiv.org/content/10.64898/2026.10.24.761556v1
AB  - Influenza A virus (IAV) remains a significant public health threat, with the need for effective vaccines and antiviral therapies remaining a high priority. In vitro testing is paramount in studying novel IAV viruses and their immunogenicity. To address this need, we developed a synthetic virology approach to rapidly prototype and test IAV mutants with altered antigenic sites. By strategically inserting restriction sites within an ambisense plasmid, we generated a tool where we can seamlessly replace either 1) the full hemagglutinin (HA), 2) the HA globular head domain to generate head/stalk chimeras or 3) the five canonical antigenic sites. The cloning inserts can be computationally designed and artificially synthesized, enabling rescue of synthetic Influenza A viruses. Using this platform we rescued IAV H1N1, H3N2 & H5N1, and went on to prototype their respective antigenic site mutants & chimeric IAVs using viral genome sequence alone. This platform could be useful for generating vaccine seed strains or to study anti-viral immunity.
ER  -

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