{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:12:25Z","timestamp":1791364345522,"version":"4.3.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Touchlight Genetics Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase the breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realize their potential. Here, we investigate influenza virus vaccines made using a closed linear DNA platform, Doggybone\u2122 DNA (dbDNA), produced by a rapid and scalable cell-free method. Influenza vaccines have mostly focussed on Haemagglutinin (HA), but the inclusion of Neuraminidase (NA) may provide additional protection. Here, we explored the potential of including NA in a dbDNA vaccine, looking at DNA optimization, mechanism and breadth of protection. We showed that DNA targeting sequences (DTS) improved immune responses against HA but not NA. We explored whether NA vaccine-induced protection against influenza virus infection was cell-mediated, but depletion of CD8 and NK cells made no impact, suggesting it was antibody-mediated. This is reflected in the restriction of protection to homologous strains of influenza virus. Importantly, we saw that including both HA and NA in a single combined vaccine did not dampen the immune response to either one. Overall, we show that linear dbDNA can induce an immune response against NA, which may offer increased protection in instances of HA mismatch where NA remains more conserved.<\/jats:p>","DOI":"10.1093\/discim\/kyad030","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T08:26:33Z","timestamp":1704270393000},"source":"Crossref","is-referenced-by-count":7,"title":["Optimizing a linear \u2018Doggybone\u2019 DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen"],"prefix":"10.1093","volume":"3","author":[{"given":"Robert F","family":"Cunliffe","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London W2 1PG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Stirling","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London W2 1PG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Razzano","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Siena , 53100 Siena , Italy"},{"name":"VisMederi srl , Siena, 53100 , Italia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valarmathy","family":"Murugaiah","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London W2 1PG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Montomoli","sequence":"additional","affiliation":[{"name":"VisMederi srl , Siena, 53100 , Italia"},{"name":"Department of Molecular and Developmental Medicine, University of Siena , 53100 Siena , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Touchlight Genetics Ltd , Hampton, TW12 2ER , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madina","family":"Wane","sequence":"additional","affiliation":[{"name":"Touchlight Genetics Ltd , Hampton, TW12 2ER , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Horton","sequence":"additional","affiliation":[{"name":"Touchlight Genetics Ltd , Hampton, TW12 2ER , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J","family":"Caproni","sequence":"additional","affiliation":[{"name":"Touchlight Genetics Ltd , Hampton, TW12 2ER , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8093-8741","authenticated-orcid":false,"given":"John S","family":"Tregoning","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London W2 1PG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"2024011212522718200_CIT0001","doi-asserted-by":"crossref","first-page":"6573","DOI":"10.1016\/j.vaccine.2021.08.010","article-title":"A Research and Development (R&D) roadmap for influenza vaccines: looking toward the future","volume":"39","author":"Moore","year":"2021","journal-title":"Vaccine"},{"key":"2024011212522718200_CIT0002","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/nbt0905-1059","article-title":"Rapid-response vaccines--does DNA offer a solution","volume":"23","author":"Forde","year":"2005","journal-title":"Nat Biotechnol"},{"key":"2024011212522718200_CIT0003","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/cei.13517","article-title":"Vaccines for COVID-19","volume":"202","author":"Tregoning","year":"2020","journal-title":"Clin Exp 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