[{"command":"settings","settings":{"pluralDelimiter":"\u0003","suppressDeprecationErrors":true,"entitySetting":{"type":"bibcite_reference","bundle":"journal_article","mapping":{"node":{"blog":"blog","class":"classes","events":"calendar","faq":"faq","link":"links","news":"news","page":"","person":"people","presentation":"presentations","software_project":"software","software_release":"software"},"bibcite_reference":{"*":"publications"},"paragraph":{"class_material":"classes"}},"viewmode":"teaser"},"user":{"uid":0,"permissionsHash":"7f1a171f8b0b5a764cab6d1b118f6329cfc3469f3145adbaf7b7495bbf60a5ea"}},"merge":true},{"command":"add_js","selector":"body","data":[{"src":"\/files\/js\/js_DOoUrEhS-bkVvWBnZGMbXVBHnh5Ov7QOD3C6k4k3980.js?scope=footer\u0026delta=0\u0026language=en\u0026theme=texasbio_eligendi\u0026include=eJzLL44vKE3KyUxOLMnMzyvWTykqLUjM0ctHFdbLzSxO1ikrzixJ1U_OzytJrSgpTcxxK83JCctMLQcAsjEbVw"}]},{"command":"insert","method":"replaceWith","selector":"#","data":"\n  \u003Cdiv class=\u0022field field--name-field-widget-title field--type-string field--label-visually_hidden field--mode-full\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EWidget Title\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003ETemperature sensitive\u003C\/div\u003E\n          \u003C\/div\u003E\n\n\u003Cul  id=\u0022list-of-posts\u0022 more_link_id=\u0022node-readmore\u0022 class=\u0022publications view-teaser grid-view\u0022\u003E\n \u003Cli\u003E\n\u003Carticle class=\u0022bibcite-reference bibcite bibcite--teaser\u0022\u003E\n  \n  \n  \n\n  \u003Cdiv class=\u0022bibcite__content\u0022\u003E\n    \u003Cdiv class=\u0022bibcite-citation\u0022\u003E\n      \u003Cdiv class=\u0022csl-bib-body\u0022\u003E\u003Cdiv class=\u0022csl-entry\u0022\u003ENogales, Aitor, John Steel, Wen-Chun Liu, Anice C Lowen, Laura Rodriguez, Kevin Chiem, Andrew Cox, et al. (2022) 2022. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/mutation-l319q-pb1-polymerase-subunit-improves-attenuation-candidate-live-attenuated\u0022 hreflang=\u0022en\u0022\u003EMutation L319Q in the PB1 Polymerase Subunit Improves Attenuation of a Candidate Live-Attenuated Influenza A Virus Vaccine.\u003C\/a\u003E\u201d. \u003Ci\u003EMicrobiology Spectrum\u003C\/i\u003E 10 (3): e0007822. https:\/\/doi.org\/10.1128\/spectrum.00078-22.\u003C\/div\u003E\u003C\/div\u003E\n  \u003C\/div\u003E\n\n  \u003Cdiv class=\u0022field field--name-publishers-version field--type-link field--label-visually_hidden field--mode-teaser\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EPublisher\u0027s Version\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/35583364\u0022\u003EPublisher\u0026#039;s Version\u003C\/a\u003E\u003C\/div\u003E\n          \u003C\/div\u003E\n                \u003Cdiv class=\u0022field--label field--abstract\u0022\u003E\n      \u003Cbutton class=\u0022btn-abstract collapsed\u0022 data-toggle=\u0022collapse\u0022 data-target=\u0022#collapseAbstract\u0022 aria-expanded=\u0022false\u0022 aria-controls=\u0022collapseAbstract\u0022\u003EAbstract \u003C\/button\u003E\n    \u003C\/div\u003E\n                  \u003Cdiv class=\u0022field--item abstract--content collapse\u0022 id=\u0022collapseAbstract\u0022 aria-expanded=\u0026quot;false\u0026quot;\u003E\u003Cp\u003EInfluenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A\/Ann Arbor\/6\/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A\/California\/04\/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the \u003Ci\u003Ein vitro\u003C\/i\u003E and \u003Ci\u003Ein vivo\u003C\/i\u003E properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain. IMPORTANCE Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concern with the current MDV used to generate the U.S.-licensed LAIV is that it is based on a virus isolated in 1960. Moreover, mutations that confer the temperature-sensitive, cold-adapted, and attenuated phenotype of the U.S. MDV resulted in low level of attenuation in the contemporary pandemic A\/California\/04\/09 H1N1 (pH1N1). Here, we show that introduction of PB1 L319Q substitution, alone or in combination with the U.S. MDV mutations, resulted in pH1N1 attenuation. These findings support the development of a novel LAIV MDV based on a contemporary pH1N1 strain as a medical countermeasure against currently circulating H1N1 IAV.\u003C\/p\u003E\n\u003C\/div\u003E\n        \n  \u003C\/div\u003E\n\u003C\/article\u003E\n\u003C\/li\u003E\n \u003Cli\u003E\n\u003Carticle class=\u0022bibcite-reference bibcite bibcite--teaser\u0022\u003E\n  \n  \n  \n\n  \u003Cdiv class=\u0022bibcite__content\u0022\u003E\n    \u003Cdiv class=\u0022bibcite-citation\u0022\u003E\n      \u003Cdiv class=\u0022csl-bib-body\u0022\u003E\u003Cdiv class=\u0022csl-entry\u0022\u003ECox, Andrew, Steven F Baker, Aitor Nogales, Luis Martinez-Sobrido, and Stephen Dewhurst. (2015) 2015. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/development-mouse-adapted-live-attenuated-influenza-virus-permits-vivo-analysis\u0022 hreflang=\u0022en\u0022\u003EDevelopment of a Mouse-Adapted Live Attenuated Influenza Virus That Permits in Vivo Analysis of Enhancements to the Safety of Live Attenuated Influenza Virus Vaccine.\u003C\/a\u003E\u201d. \u003Ci\u003EJournal of Virology\u003C\/i\u003E 89 (6): 3421-6. https:\/\/doi.org\/10.1128\/JVI.02636-14.\u003C\/div\u003E\u003C\/div\u003E\n  \u003C\/div\u003E\n\n  \u003Cdiv class=\u0022field field--name-publishers-version field--type-link field--label-visually_hidden field--mode-teaser\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EPublisher\u0027s Version\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25552727\u0022\u003EPublisher\u0026#039;s Version\u003C\/a\u003E\u003C\/div\u003E\n          \u003C\/div\u003E\n                \u003Cdiv class=\u0022field--label field--abstract\u0022\u003E\n      \u003Cbutton class=\u0022btn-abstract collapsed\u0022 data-toggle=\u0022collapse\u0022 data-target=\u0022#collapseAbstract\u0022 aria-expanded=\u0022false\u0022 aria-controls=\u0022collapseAbstract\u0022\u003EAbstract \u003C\/button\u003E\n    \u003C\/div\u003E\n                  \u003Cdiv class=\u0022field--item abstract--content collapse\u0022 id=\u0022collapseAbstract\u0022 aria-expanded=\u0026quot;false\u0026quot;\u003E\u003Cp\u003EThe live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs.\u003C\/p\u003E\n\u003C\/div\u003E\n        \n  \u003C\/div\u003E\n\u003C\/article\u003E\n\u003C\/li\u003E\n \u003Cli\u003E\n\u003Carticle class=\u0022bibcite-reference bibcite bibcite--teaser\u0022\u003E\n  \n  \n  \n\n  \u003Cdiv class=\u0022bibcite__content\u0022\u003E\n    \u003Cdiv class=\u0022bibcite-citation\u0022\u003E\n      \u003Cdiv class=\u0022csl-bib-body\u0022\u003E\u003Cdiv class=\u0022csl-entry\u0022\u003ENogales, Aitor, Laura Rodriguez, Caroline Chauch\u00e9, Kai Huang, Emma C Reilly, David J Topham, Pablo R Murcia, Colin R Parrish, and Luis Martinez-Sobrido. (2017) 2017. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/temperature-sensitive-live-attenuated-canine-influenza-virus-h3n8-vaccine\u0022 hreflang=\u0022en\u0022\u003ETemperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine.\u003C\/a\u003E\u201d. \u003Ci\u003EJournal of Virology\u003C\/i\u003E 91 (4). https:\/\/doi.org\/10.1128\/JVI.02211-16.\u003C\/div\u003E\u003C\/div\u003E\n  \u003C\/div\u003E\n\n  \u003Cdiv class=\u0022field field--name-publishers-version field--type-link field--label-visually_hidden field--mode-teaser\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EPublisher\u0027s Version\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27928017\u0022\u003EPublisher\u0026#039;s Version\u003C\/a\u003E\u003C\/div\u003E\n          \u003C\/div\u003E\n                \u003Cdiv class=\u0022field--label field--abstract\u0022\u003E\n      \u003Cbutton class=\u0022btn-abstract collapsed\u0022 data-toggle=\u0022collapse\u0022 data-target=\u0022#collapseAbstract\u0022 aria-expanded=\u0022false\u0022 aria-controls=\u0022collapseAbstract\u0022\u003EAbstract \u003C\/button\u003E\n    \u003C\/div\u003E\n                  \u003Cdiv class=\u0022field--item abstract--content collapse\u0022 id=\u0022collapseAbstract\u0022 aria-expanded=\u0026quot;false\u0026quot;\u003E\u003Cp\u003E\u003Cb\u003EUNLABELLED: \u003C\/b\u003ECanine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33\u00b0C but is impaired at temperatures of 37 to 39\u00b0C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cb\u003EIMPORTANCE: \u003C\/b\u003ETwo influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.\u003C\/p\u003E\n\u003C\/div\u003E\n        \n  \u003C\/div\u003E\n\u003C\/article\u003E\n\u003C\/li\u003E\n\u003C\/ul\u003E\n  \u003Cnav role=\u0022navigation\u0022 aria-labelledby=\u0022pagination-for-live-attenuated-vaccines-temperature-sensitive-publications-lop\u0022 id=pager-heading\u003E\n    \u003Ch3 id=\u0022pagination-for-live-attenuated-vaccines-temperature-sensitive-publications-lop\u0022 class=\u0022visually-hidden\u0022\u003Epagination for live attenuated vaccines temperature sensitive publications lop\u003C\/h3\u003E\n    \u003Cul class=\u0022js-pager__items pager-mini\u0022\u003E\n            \u003Cli class=\u0022current\u0022\u003E\n        \u003Cspan aria-live=\u0022polite\u0022\u003E\n            \u003Cspan class=\u0022visually-hidden\u0022\u003ELive-attenuated vaccines - Temperature sensitive - Publications LOP\u003C\/span\u003E\n            1 of 4\n          \u003C\/span\u003E      \u003C\/li\u003E\n              \u003Cli\u003E\n          \u003Ca href=\u0022\/lms-lab\/refresh-widget-content\/2947?page=1\u0026amp;selector=list-of-posts\u0026amp;pagerid=pager-heading\u0026amp;moreid=node-readmore\u0022 class=\u0022use-ajax next\u0022 rel=\u0022next\u0022\u003E\u003Cspan aria-hidden=\u0022true\u0022\u003E\u203a\u203a\u003C\/span\u003E\u003Cspan class=\u0022visually-hidden\u0022\u003ENext page\u003C\/span\u003E\u003C\/a\u003E\n        \u003C\/li\u003E\n          \u003C\/ul\u003E\n  \u003C\/nav\u003E\n\n\u003Cdiv class=\u0022node-readmore\u0022 id=node-readmore\u003E\u003C\/div\u003E\n","settings":null},{"command":"insert","method":"replaceWith","selector":"#","data":"","settings":null},{"command":"insert","method":"replaceWith","selector":"#","data":"","settings":null},{"command":"insert","method":"replaceWith","selector":".field--name-field-widget-title","data":"","settings":null}]