{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:40:29Z","timestamp":1787611229850,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Office of the Assistant Secretary of Defense for Health Affairs","award":["W81XWH-17-1-0430"],"award-info":[{"award-number":["W81XWH-17-1-0430"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated \u22652-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Serosusceptible subjects aged 18\u201349 years were randomized to receive 2 doses (108\u2013109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The vaccine was well tolerated at all dose levels. Against Belgium2015, \u2265 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%\u201356.7%) of subjects following a single 108 TCID50 M2SR dose and among 80.6% (95% CI, 61.4%\u201392.3%) after 109 dose (P &amp;lt; .001). A single 109 TCID50 dose of M2SR generated \u22654-fold hemagglutination inhibition antibody seroconversion against the vaccine strain in 71% (95% CI, 52.0%\u201385.8%) of recipients. Mucosal and cellular immune responses were also induced.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results indicate that M2SR may provide substantial protection against infection with highly drifted strains of H3N2 influenza.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT03999554.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiac433","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T22:05:08Z","timestamp":1667426708000},"page":"103-112","source":"Crossref","is-referenced-by-count":19,"title":["Intranasal M2SR (M2-Deficient Single Replication) H3N2 Influenza Vaccine Provides Enhanced Mucosal and Serum Antibodies in Adults"],"prefix":"10.1093","volume":"227","author":[{"given":"Joseph","family":"Eiden","sequence":"first","affiliation":[{"name":"FluGen, Inc , Madison, Wisconsin , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Fierro","sequence":"additional","affiliation":[{"name":"Johnson County Clin-Trials , Lenexa, Kansas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Research Centers of America , Hollywood, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Adams","sequence":"additional","affiliation":[{"name":"Alliance for Multispecialty Research , Lexington, Kentucky , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly J","family":"Ellis","sequence":"additional","affiliation":[{"name":"Alliance for Multispecialty Research , Norfolk, Virginia , 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