tetano
Editor, Senior Moderator
Cell Rep
. 2026 Nov 6:118244.
doi: 10.1016/j.celrep.2026.118244. Online ahead of print.
Anass Abbad 1 , Temima Yellin 1 , Juan Manuel Carreño 1 , Justine S McPartlan 2 , Poulami Talukder 2 , Eduard Puente-Massaguer 1 , Irene González-Domínguez 3 , Michael Scherm 1 , Dominika Bielak 1 , Brian Lerman 1 , Christian W Mandl 2 , Jasdave S Chahal 2 , Florian Krammer 4
Affiliations Expand
Seasonal influenza vaccines require annual reformulation due to antigenic drift and provide suboptimal protection. Here, we evaluate self-amplifying mRNA (samRNA) vaccines encoding chimeric (cHA) and mosaic (mHA) hemagglutinins representing influenza A virus HA phylogenetic groups 1 and 2. Following prime-boost immunization, group 1 cHA vaccines (cH8/1-cH5/1) elicit broad cross-reactive antibodies and confer complete protection against diverse H1N1 strains covering decades of antigenic drift. Group 2 vaccines (cH4/3-cH15/3 and mH10/3-mH14/3) provide comparable breadth against multiple H3N2 strains and heterosubtypic H7N9 challenge, with cHA samRNA showing superior cross-group protection. Protection is associated with Fc-mediated effector functions and CD4+ T cell responses, with minimal hemagglutination inhibition and neutralizing titers. Passive serum transfer confirms antibody-mediated protection independent of cellular immunity. Protective immunity is maintained at doses as low as 0.4 μg, demonstrating the dose-sparing advantage of the samRNA platform. These results support samRNA-delivered cHA and mHA antigens as promising candidates for broadly protective influenza vaccines.
Keywords: ADCC; CP: immunology; broadly protective vaccine; chimeric hemagglutinin; hemagglutinin; influenza; mRNA vaccine; mosaic hemagglutinin; self-amplifying RNA; stalk antibodies.
. 2026 Nov 6:118244.
doi: 10.1016/j.celrep.2026.118244. Online ahead of print.
Self-amplifying RNA vaccines encoding chimeric and mosaic hemagglutinins confer immunity against phylogenetically diverse influenza A viruses
Anass Abbad 1 , Temima Yellin 1 , Juan Manuel Carreño 1 , Justine S McPartlan 2 , Poulami Talukder 2 , Eduard Puente-Massaguer 1 , Irene González-Domínguez 3 , Michael Scherm 1 , Dominika Bielak 1 , Brian Lerman 1 , Christian W Mandl 2 , Jasdave S Chahal 2 , Florian Krammer 4
Affiliations Expand
- PMID: 42994435
- DOI: 10.1016/j.celrep.2026.118244
Abstract
Seasonal influenza vaccines require annual reformulation due to antigenic drift and provide suboptimal protection. Here, we evaluate self-amplifying mRNA (samRNA) vaccines encoding chimeric (cHA) and mosaic (mHA) hemagglutinins representing influenza A virus HA phylogenetic groups 1 and 2. Following prime-boost immunization, group 1 cHA vaccines (cH8/1-cH5/1) elicit broad cross-reactive antibodies and confer complete protection against diverse H1N1 strains covering decades of antigenic drift. Group 2 vaccines (cH4/3-cH15/3 and mH10/3-mH14/3) provide comparable breadth against multiple H3N2 strains and heterosubtypic H7N9 challenge, with cHA samRNA showing superior cross-group protection. Protection is associated with Fc-mediated effector functions and CD4+ T cell responses, with minimal hemagglutination inhibition and neutralizing titers. Passive serum transfer confirms antibody-mediated protection independent of cellular immunity. Protective immunity is maintained at doses as low as 0.4 μg, demonstrating the dose-sparing advantage of the samRNA platform. These results support samRNA-delivered cHA and mHA antigens as promising candidates for broadly protective influenza vaccines.
Keywords: ADCC; CP: immunology; broadly protective vaccine; chimeric hemagglutinin; hemagglutinin; influenza; mRNA vaccine; mosaic hemagglutinin; self-amplifying RNA; stalk antibodies.