{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T01:55:11Z","timestamp":1775008511425,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["AI153936\u201001"],"award-info":[{"award-number":["AI153936\u201001"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015853","name":"Rochester Institute of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015853","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>Nontypeable <jats:italic>Haemophilus\u2009influenzae<\/jats:italic> (<jats:italic>NTHi<\/jats:italic>) has emerged as a dominant mucosal pathogen causing acute otitis media (AOM) in children, acute sinusitis in children and adults, and acute exacerbations of chronic bronchitis in adults. Consequently, there is an urgent need to develop a vaccine to protect against <jats:italic>NTHi<\/jats:italic> infection. A multi\u2010component vaccine will be desirable to avoid emergence of strains expressing modified proteins allowing vaccine escape. Protein D (PD), outer membrane protein (OMP) 26, and Protein 6 (P6) are leading protein vaccine candidates against <jats:italic>NTHi<\/jats:italic>. In pre\u2010clinical research using mouse models, we found that recombinantly expressed PD, OMP26, and P6 induce robust antibody responses after vaccination as individual vaccines, but when PD and OMP26 were combined into a single vaccine formulation, PD antibody levels were significantly lower. We postulated that PD and OMP26 physiochemically interacted to mask PD antigenic epitopes resulting in the observed effect on antibody response. However, column chromatography and mass spectrometry analysis did not support our hypothesis. We postulated that the effect might be <jats:italic>in\u2009vivo<\/jats:italic> through the mechanism of protein vaccine immunologic antigenic competition. We found when PD and OMP26 were injected into the same leg or separate legs of mice, so that antigens were immunologically processed at the same or different regional lymph nodes, respectively, antibody levels to PD were significantly lower with same leg vaccination. Different leg vaccination produced PD antibody levels quantitatively similar to vaccination with PD alone. We conclude that mixing PD and OMP26 into a single vaccine formulation requires further formulation studies.<\/jats:p>","DOI":"10.1002\/2211-5463.13498","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T09:29:45Z","timestamp":1666258185000},"page":"2191-2202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>Haemophilus influenzae<\/i> Protein D antibody suppression in a multi\u2010component vaccine formulation"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-4646","authenticated-orcid":false,"given":"Lea V.","family":"Michel","sequence":"first","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Immunology Rochester General Hospital Research Institute  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L.","family":"Gleghorn","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melody","family":"Holmquist","sequence":"additional","affiliation":[{"name":"National Technical Institute for the Deaf Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Pryharski","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Immunology Rochester General Hospital Research Institute  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janai","family":"Perdue","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth P.","family":"Jones","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niaya","family":"Jackson","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Pilo","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kasper","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Labbe","sequence":"additional","affiliation":[{"name":"School of Chemistry and Materials Science Rochester Institute of Technology  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Pichichero","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Immunology Rochester General Hospital Research Institute  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3181c1bc48"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31829e3779"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3181950c74"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.7.9.1299"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318060cc19"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002383"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2303.161552"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199702001-00002"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70734-0"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00097"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000023"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S3385"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)00097-7"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2019.05.007"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2018.09.015"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00089-15"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318184dba2"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2016.1156539"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00288-7"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000827"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2012.00967.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00678-21"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.7.1.13351"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.08.063"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.1.119-125.1991"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.06.004"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.5.2272-2278.1998"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.11.4848-4854.1994"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4691-4699.2003"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00116\u201019"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.05.079"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-890-0:571"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809275106"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijms.2020.116451"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.4578"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1265"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.130.4.821"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3266"},{"key":"e_1_2_11_40_1","first-page":"943","article-title":"Studies on antigenic competition. 3. Effect on antigenic competition on antibody affinity","volume":"26","author":"Kim YT","year":"1974","journal-title":"Immunology"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.135.4.2319"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(94)90125-2"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.13498","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.13498","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.13498","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T09:22:49Z","timestamp":1692350569000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.13498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,28]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/2211-5463.13498"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.13498","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,28]]},"assertion":[{"value":"2022-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}