tetano
Editor, Senior Moderator
Cell Rep Med
. 2026 Nov 5:103131.
doi: 10.1016/j.xcrm.2026.103131. Online ahead of print.
Joanne Marie M Del Rosario 1 , Sneha Vishwanath 2 , Simon D W Frost 3 , Sneha B Sujit 1 , Sruthika K Ashokan 1 , Robert Vendramelli 4 , Matteo Ferrari 1 , George W Carnell 5 , Lucrezia Vianello 6 , Matteo Pagliari 7 , Sami Ramzi 8 , Valentina Maria Panzarin 6 , Elisa Mazzacan 6 , Andrea Fortin 6 , Marta Vascellari 9 , Thang Truong 4 , Paul Tonks 2 , Ana Liza Ortiz 10 , Chloe Qingzhou Huang 2 , Sebastian Einhauser 11 , Michael Schachtner 11 , Benedikt Asbach 11 , Daniel Matthew L Storisteanu 2 , Nigel J Temperton 12 , Matthew N Davies 1 , David Moss 1 , Rebecca Kinsley 1 , Ralf Wagner 13 , Darwyn Kobasa 14 , Francesco Bonfante 6 , Jonathan L Heeney 15
Affiliations Expand
Influenza A/H5Nx viruses continue to diversify and undergo gene reassortment as they infect avian and mammalian hosts worldwide. The severity of human infections varies substantially between different H5 clades and neuraminidase (NA) reassortants, creating unpredictable pandemic risk. Existing H5 vaccines, typically based on a single hemagglutinin (HA) strain, cannot keep pace with this natural variation. To address this problem, we computationally engineer HA, NA, and M2 antigens representing the global antigenic space of circulating H5Nx viruses, prioritizing N1 and N6 subtypes associated with the highest threat in humans. The resulting digitally immune-optimized mRNA vaccine, DVX-panH5Nx, elicits broad HA neutralization and NA inhibition across divergent clades in mice and ferrets. Compared to WHO candidate vaccine viruses (CVVs), DVX-panH5Nx confers superior protection against antigenically distinct H5N1 challenges spanning two decades of viral evolution, demonstrating that computationally designed multivalent antigen vaccines can overcome natural influenza diversification and provide a scalable strategy for pre-pandemic preparedness.
Keywords: broad cross-clade neutralization; computationally engineered vaccine design; digital immune optimization; influenza A/H5Nx; neuraminidase inhibition; next-generation influenza vaccine; pandemic preparedness.
. 2026 Nov 5:103131.
doi: 10.1016/j.xcrm.2026.103131. Online ahead of print.
Broad vaccine protection against globally diverse influenza A/H5Nx viruses
Joanne Marie M Del Rosario 1 , Sneha Vishwanath 2 , Simon D W Frost 3 , Sneha B Sujit 1 , Sruthika K Ashokan 1 , Robert Vendramelli 4 , Matteo Ferrari 1 , George W Carnell 5 , Lucrezia Vianello 6 , Matteo Pagliari 7 , Sami Ramzi 8 , Valentina Maria Panzarin 6 , Elisa Mazzacan 6 , Andrea Fortin 6 , Marta Vascellari 9 , Thang Truong 4 , Paul Tonks 2 , Ana Liza Ortiz 10 , Chloe Qingzhou Huang 2 , Sebastian Einhauser 11 , Michael Schachtner 11 , Benedikt Asbach 11 , Daniel Matthew L Storisteanu 2 , Nigel J Temperton 12 , Matthew N Davies 1 , David Moss 1 , Rebecca Kinsley 1 , Ralf Wagner 13 , Darwyn Kobasa 14 , Francesco Bonfante 6 , Jonathan L Heeney 15
Affiliations Expand
- PMID: 42987826
- DOI: 10.1016/j.xcrm.2026.103131
Abstract
Influenza A/H5Nx viruses continue to diversify and undergo gene reassortment as they infect avian and mammalian hosts worldwide. The severity of human infections varies substantially between different H5 clades and neuraminidase (NA) reassortants, creating unpredictable pandemic risk. Existing H5 vaccines, typically based on a single hemagglutinin (HA) strain, cannot keep pace with this natural variation. To address this problem, we computationally engineer HA, NA, and M2 antigens representing the global antigenic space of circulating H5Nx viruses, prioritizing N1 and N6 subtypes associated with the highest threat in humans. The resulting digitally immune-optimized mRNA vaccine, DVX-panH5Nx, elicits broad HA neutralization and NA inhibition across divergent clades in mice and ferrets. Compared to WHO candidate vaccine viruses (CVVs), DVX-panH5Nx confers superior protection against antigenically distinct H5N1 challenges spanning two decades of viral evolution, demonstrating that computationally designed multivalent antigen vaccines can overcome natural influenza diversification and provide a scalable strategy for pre-pandemic preparedness.
Keywords: broad cross-clade neutralization; computationally engineered vaccine design; digital immune optimization; influenza A/H5Nx; neuraminidase inhibition; next-generation influenza vaccine; pandemic preparedness.