{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:29:44Z","timestamp":1790792984459,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vaccine platforms enable fast development, testing, and manufacture of more affordable vaccines. Here, we evaluated Generalized Modules for Membrane Antigens (GMMA), outer membrane vesicles (OMVs) generated by genetically modified Gram\u2010negative bacteria, as a vaccine platform for viral pathogens. Influenza A virus hemagglutinin (HA), either physically mixed with GMMA (HA+STmGMMA mix), or covalently linked to GMMA surface (HA\u2010STmGMMA conjugate), significantly increased antigen\u2010specific humoral and cellular responses, with HA\u2010STmGMMA conjugate inducing further enhancement than HA+STmGMMA mix. HA\u2010STmGMMA conjugate protected mice from lethal challenge. The versatility for this platform was confirmed by conjugation of rabies glycoprotein (RABVG) onto GMMA through the same method. RABVG+STmGMMA mix and RABVG\u2010STmGMMA conjugate exhibited similar humoral and cellular response patterns and protection efficacy as the HA formulations, indicating relatively consistent responses for different vaccines based on the GMMA platform. Comparing to soluble protein, GMMA was more efficiently taken up in vivo and exhibited a B\u2010cell preferential uptake in the draining lymph nodes (LNs). Together, GMMA enhances immunity against viral antigens, and the platform works well with different antigens while retaining similar immunomodulatory patterns. The findings of our study imply the great potential of GMMA\u2010based vaccine platform also against viral infectious diseases.<\/jats:p>","DOI":"10.1002\/jev2.12247","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:21:04Z","timestamp":1668471664000},"source":"Crossref","is-referenced-by-count":18,"title":["Generalized Modules for Membrane Antigens (GMMA), an outer membrane vesicle\u2010based vaccine platform, for efficient viral antigen delivery"],"prefix":"10.1002","volume":"11","author":[{"given":"Kai","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Palmieri","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH) S.r.l.  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karnyart","family":"Samnuan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Ricchetti","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH) S.r.l.  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Oldrini","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH) S.r.l.  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Wu","sequence":"additional","affiliation":[{"name":"Animal and Plant Health Agency (APHA), OIE Rabies Reference Laboratory  New Haw, Addlestone Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Thorne","sequence":"additional","affiliation":[{"name":"Animal and Plant Health Agency (APHA), OIE Rabies Reference Laboratory  New Haw, Addlestone Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Fooks","sequence":"additional","affiliation":[{"name":"Animal and Plant Health Agency (APHA), OIE Rabies Reference Laboratory  New Haw, Addlestone Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine M.","family":"McElhinney","sequence":"additional","affiliation":[{"name":"Animal and Plant Health Agency (APHA), OIE Rabies Reference Laboratory  New Haw, Addlestone Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooman","family":"Goharriz","sequence":"additional","affiliation":[{"name":"Animal and Plant Health Agency (APHA), OIE Rabies Reference Laboratory  New Haw, Addlestone Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Golding","sequence":"additional","affiliation":[{"name":"Animal and Plant Health Agency (APHA), OIE Rabies Reference Laboratory  New Haw, Addlestone Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Micoli","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH) S.r.l.  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/hs.2019.0148"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678-775720140140"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.629090"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v2i0.20181"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c00326"},{"key":"e_1_2_9_7_1","unstructured":"Centers for Disease Control and Prevention Flu Vaccine and People with Egg Allergies. (2020).https:\/\/www.cdc.gov\/flu\/prevent\/egg-allergies.htm#:~:text=Changes%3A egg%20should%20receive%20flu%20vaccine"},{"key":"e_1_2_9_8_1","volume-title":"World Organization for Animal Health","author":"Chapter O.","year":"2018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22087-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.11.089"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.7b01173"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1753-6561-5-S1-P62"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.09.073"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031309"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134478"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2017.05.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.05.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2010.11.024"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000895"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00356"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3837"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coisb.2017.05.016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201800376"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2010.11.002"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020242"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.03.010"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.10.083"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00335"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmats.2020.00202"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp2005630"},{"key":"e_1_2_9_32_1","first-page":"3122","article-title":"GMMA\u2010Based Vaccines: The Known and The Unknown","author":"Mancini F.","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124416"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17409-9"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1807655115"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8030540"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.09.009"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01884"},{"key":"e_1_2_9_39_1","unstructured":"World Health Organization Serological detection of avian influenza A(H7N9) virus infections by modified horse red blood cells haemagglutination\u2010inhibition assay. (2013).https:\/\/www.who.int\/publications\/m\/item\/serological-detection-of-avian-influenza-a(h7n9)-virus-infections-by-modified-horse-red-blood-cells-haemagglutination-inhibition-assay"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.01.028"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1129"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.566570"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00023-16"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.2165\/11530550-000000000-00000"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.03.006"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00783"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.781280"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400395"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cww086"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821317116"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/000349-0"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/5697149"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3469"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12247","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jev2.12247","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.12247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:38:21Z","timestamp":1760621901000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.12247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/jev2.12247"],"URL":"https:\/\/doi.org\/10.1002\/jev2.12247","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11]]},"article-number":"e12247"}}