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Such increased breadth would not only improve seasonal vaccines but may afford \u2018universal\u2019 protection against influenza subtypes, including those with pandemic potential. Here, we describe a \u2018beads-on-a-string (BOAS)\u2019 immunogen that tandemly links up to eight distinct hemagglutinin (HA) head domains from circulating and non-circulating influenzas. These BOAS are immunogenic in the murine model and elicit comparable serum responses to each individual component. Notably, we also find that BOAS elicit cross-reactive responses to influenza subtypes not included in the immunizing immunogen. Furthermore, BOAS conjugation to protein-based ferritin nanoparticles does not significantly augment serum responses suggesting that our BOAS platform is sufficient for eliciting cross-reactive responses without off-target effects induced by the nanoparticle scaffold. Finally, vaccination with a mixture of the same HA head domains is not sufficient to elicit the same neutralization profile as the BOAS immunogens or nanoparticles. This mix-and-match immunogen design strategy is a robust platform for eliciting responses to multiple influenza subtypes via a single immunogen, and a potential platform for other viral glycoproteins.<\/jats:p>","DOI":"10.7554\/elife.97364","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T07:25:19Z","timestamp":1714116319000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.97364","source":"Crossref","is-referenced-by-count":4,"title":["A modular platform to display multiple hemagglutinin subtypes on a single immunogen"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9440-9656","authenticated-orcid":true,"given":"Dana","family":"Thornlow Lamson","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/053r20n13","id-type":"ROR","asserted-by":"publisher"}],"name":"Ragon Institute of Mass General, MIT, and Harvard","place":["Cambridge, United 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