{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:26:01Z","timestamp":1740147961637,"version":"3.37.3"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,8,2]],"date-time":"2014-08-02T00:00:00Z","timestamp":1406937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0600509"],"award-info":[{"award-number":["G0600509"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Internal funding NIBSC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2014,11]]},"abstract":"Background<\/jats:title>Annual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA<\/jats:styled-content>) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses.<\/jats:p><\/jats:sec>Objectives<\/jats:title>It has been shown elsewhere that mutations introduced in the non\u2010coding region of influenza genome segments can upregulate protein expression. Our objective was to assess a virus based on the laboratory strain A\/PR<\/jats:styled-content>\/8\/34 (PR<\/jats:styled-content>8) containing a modified 3\u2032 non\u2010coding region of RNA<\/jats:styled-content> segment 4 (haemagglutinin).<\/jats:p><\/jats:sec>Methods<\/jats:title>NIBRG<\/jats:styled-content>\u201093 was generated using reverse genetics. HA<\/jats:styled-content> protein expression and growth properties were assessed. The virus phenotype suggested that it could be a candidate for use as a live attenuated vaccine, so in vivo<\/jats:italic> studies were performed to assess its suitability.<\/jats:p><\/jats:sec>Results<\/jats:title>NIBRG<\/jats:styled-content>\u201093 virus has enhanced haemagglutinin production and is significantly attenuated. Electron microscopy (EM<\/jats:styled-content>) shows that the modified virus produces a large proportion of \u2018virus\u2010like particles\u2019 that consist of budded cell membrane covered in HA<\/jats:styled-content> but lacking M1 protein. The virus was shown to be attenuated in mice and offered complete protection against lethal challenge.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>We demonstrate that NIBRG<\/jats:styled-content>\u201093 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.<\/jats:p><\/jats:sec>","DOI":"10.1111\/irv.12274","type":"journal-article","created":{"date-parts":[[2014,8,2]],"date-time":"2014-08-02T06:29:13Z","timestamp":1406960953000},"page":"605-612","source":"Crossref","is-referenced-by-count":5,"title":["A promoter mutation in the haemagglutinin segment of influenza A virus generates an effective candidate live attenuated vaccine"],"prefix":"10.1111","volume":"8","author":[{"given":"Ruth","family":"Harvey","sequence":"first","affiliation":[{"name":"National Institute for Biological Standards and Control Medicines and Healthcare products Regulatory Agency Potters Bar UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"National Institute for Biological Standards and Control Medicines and Healthcare products Regulatory Agency Potters Bar UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsty","family":"MacLellan\u2010Gibson","sequence":"additional","affiliation":[{"name":"National Institute for Biological Standards and Control Medicines and Healthcare products Regulatory Agency Potters Bar UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S.","family":"Robertson","sequence":"additional","affiliation":[{"name":"National Institute for Biological Standards and Control Medicines and Healthcare products Regulatory Agency Potters Bar UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Othmar G.","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"National Institute for Biological Standards and Control Medicines and Healthcare products Regulatory Agency Potters Bar UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8,2]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(03)00071-9"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2010.00183.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.08.054"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.09.006"},{"key":"e_1_2_5_6_1","first-page":"1046","article-title":"Promoter elements in the influenza vRNA terminal structure","volume":"2","author":"Flick R","year":"1996","journal-title":"RNA"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-76-7-1709"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036241"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.09.050"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2009.00082.x"},{"key":"e_1_2_5_11_1","first-page":"227","article-title":"The method of \u2018right and wrong cases\u2019 (\u2018constant stimuli\u2019) without Gauss's formula","volume":"2","author":"Spearman C","year":"1908","journal-title":"Br J Psychol"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01863914"},{"key":"e_1_2_5_13_1","doi-asserted-by":"crossref","unstructured":"HsuJC(1996).Multiple Comparisons Theory and methods. 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