{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T23:42:42Z","timestamp":1780789362322,"version":"3.54.1"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/IN\/EU-INF\/15\/RV\/19-20"],"award-info":[{"award-number":["BT\/IN\/EU-INF\/15\/RV\/19-20"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004541","name":"Ministry of Education, India","doi-asserted-by":"publisher","award":["UAY IISc_005"],"award-info":[{"award-number":["UAY IISc_005"]}],"id":[{"id":"10.13039\/501100004541","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/INF\/22\/SP22844\/2017SM"],"award-info":[{"award-number":["BT\/INF\/22\/SP22844\/2017SM"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["DBT\/JRF\/BET-18\/I\/2018\/AL\/168"],"award-info":[{"award-number":["DBT\/JRF\/BET-18\/I\/2018\/AL\/168"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-005948"],"award-info":[{"award-number":["INV-005948"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Current influenza vaccines need to be updated annually due to mutations in the globular head of the viral surface protein, hemagglutinin (HA). To address this, vaccine candidates have been designed based on the relatively conserved HA stem domain and have shown protective efficacy in animal models. Oligomerization of the antigens either by fusion to oligomerization motifs or display on self-assembling nanoparticle scaffolds, can induce more potent immune responses compared to the corresponding monomeric antigen due to multivalent engagement of B-cells. Since nanoparticle display can increase manufacturing complexity, and often involves one or more mammalian cell expressed components, it is important to characterize and compare various display and oligomerization scaffolds. Using a structure guided approach, we successfully displayed multiple copies of a previously designed soluble, trimeric influenza stem domain immunogen, pH1HA10, on the ferritin like protein, MsDps2 (12 copies), Ferritin (24 copies) and Encapsulin (180 copies). All proteins were expressed in\n                    <jats:italic>Escherichia coli.<\/jats:italic>\n                    The nanoparticle fusion immunogens were found to be well folded and bound to the influenza stem directed broadly neutralizing antibodies with high affinity. An 8.5 \u00c5 Cryo-EM map of Msdps2-pH1HA10 confirmed the successful design of the nanoparticle fusion immunogen. Mice immunization studies with the soluble trimeric stem and nanoparticle fusion constructs revealed that all of them were immunogenic, and protected mice against homologous (A\/Belgium\/145-MA\/2009) and heterologous (A\/Puerto Rico\/8\/1934) challenge with 10MLD\n                    <jats:sub>50<\/jats:sub>\n                    mouse adapted virus. Although nanoparticle display conferred a small but statistically significant improvement in protection relative to the soluble trimer in a homologous challenge, heterologous protection was similar in both nanoparticle-stem immunized and trimeric stem immunized groups. Such rapidly producible, bacterially expressed antigens and nanoparticle scaffolds are useful modalities to tackle future influenza pandemics.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.890622","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T07:10:45Z","timestamp":1654240245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Comparative Immunogenicity of Bacterially Expressed Soluble Trimers and Nanoparticle Displayed Influenza Hemagglutinin Stem Immunogens"],"prefix":"10.3389","volume":"13","author":[{"given":"Uddipan","family":"Kar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Khaleeq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuraj","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorvi","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkada Subramanian","family":"Vignesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Upadhyaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mili","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghadiyaram","family":"Chakshusmathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somnath","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavan","family":"Varadarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1512.091413","article-title":"Estimates of the Prevalence of Pandemic (H1N1) 2009, United States, April-July 2009","volume":"15","author":"Reed","year":"2009","journal-title":"Emerg Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1003657","DOI":"10.1371\/journal.ppat.1003657","article-title":"New World Bats Harbor Diverse Influenza A Viruses","volume":"9","author":"Tong","year":"2013","journal-title":"PloS Pathog"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3362","article-title":"Enabling the \u201cHost Jump\u201d: Structural Determinants of Receptor-Binding Specificity in Influenza A Viruses","volume":"12","author":"Shi","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.07.046","article-title":"A Review of Vaccine Research and Development: Human Acute Respiratory Infections","volume":"23","author":"Girard","year":"2005","journal-title":"Vaccine"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01235-07","article-title":"Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated From Humans","volume":"81","author":"Belser","year":"2007","journal-title":"J Virol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1146\/annurev-med-120611-145115","article-title":"Toward a Universal Influenza Virus Vaccine: Prospects and Challenges","volume":"64","author":"Pica","year":"2013","journal-title":"Annu Rev Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.03.085","article-title":"Universal Influenza Vaccines: Shifting to Better Vaccines","volume":"34","author":"Berlanda Scorza","year":"2016","journal-title":"Vaccine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.immuni.2017.09.007","article-title":"The Pathway to a Universal Influenza Vaccine","volume":"47","author":"Paules","year":"2017","journal-title":"Immunity"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.7.927","article-title":"Baculovirus-Expressed Influenza Vaccine. 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