[{"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\u003EDevelopment of inactivated and live-attenuated vaccines\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\u003EHuang, Wei-Chiao, Kevin Chiem, Luis Martinez-Sobrido, and Jonathan F Lovell. (2022) 2022. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/intranasal-immunization-liposome-displayed-receptor-binding-domain-induces-mucosal\u0022 hreflang=\u0022en\u0022\u003EIntranasal Immunization With Liposome-Displayed Receptor-Binding Domain Induces Mucosal Immunity and Protection Against SARS-CoV-2.\u003C\/a\u003E\u201d. \u003Ci\u003EPathogens (Basel, Switzerland)\u003C\/i\u003E 11 (9). https:\/\/doi.org\/10.3390\/pathogens11091035.\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\/36145467\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 global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to efforts in developing effective vaccine approaches. Currently, approved coronavirus disease 2019 (COVID-19) vaccines are administered through an intramuscular (I.M.) route. Here, we show that the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD), when displayed on immunogenic liposomes, can be intranasally (I.N.) administered, resulting in the production of antigen-specific IgA and antigen-specific cellular responses in the lungs. Following I.N. immunization, antigen-presenting cells of the lungs took up liposomes displaying the RBD. K18 human ACE2-transgenic mice that were immunized I.M or I.N with sub-microgram doses of RBD liposomes and that were then challenged with SARS-CoV-2 had a reduced viral load in the early course of infection, with I.M. achieving complete viral clearance. Nevertheless, both vaccine administration routes led to full protection against lethal viral infection, demonstrating the potential for the further exploration and optimization of I.N immunization with liposome-displayed antigen vaccines.\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\u003EJiao, Yang, Wei-Chiao Huang, Kevin Chiem, Yiting Song, Jingyu Sun, Shubhada K Chothe, Shiqi Zhou, et al. (2023) 2023. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/sars-cov-2-protein-nanoparticle-vaccines-formed-situ-lyophilized-lipids\u0022 hreflang=\u0022en\u0022\u003ESARS-CoV-2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids.\u003C\/a\u003E\u201d. \u003Ci\u003ESmall (Weinheim an Der Bergstrasse, Germany)\u003C\/i\u003E, e2304534. https:\/\/doi.org\/10.1002\/smll.202304534.\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\/37849036\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 receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice\u00a0elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates.\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\u003EYe, Chengjin, Jun-Gyu Park, Kevin Chiem, Piyush Dravid, Anna Allu\u00e9-Guardia, Andreu Garcia-Vilanova, Paula Pino Tamayo, et al. (2023) 2023. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/immunization-recombinant-accessory-protein-deficient-sars-cov-2-protects-against-0\u0022 hreflang=\u0022en\u0022\u003EImmunization With Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects Against Lethal Challenge and Viral Transmission.\u003C\/a\u003E\u201d. \u003Ci\u003EMicrobiology Spectrum\u003C\/i\u003E, e0065323. https:\/\/doi.org\/10.1128\/spectrum.00653-23.\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\/37191507\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\u003ESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide coronavirus disease 2019 (COVID-19) pandemic. Despite the high efficacy of the authorized vaccines, there may be uncertain and unknown side effects or disadvantages associated with current vaccination approaches. Live-attenuated vaccines (LAVs) have been shown to elicit robust and long-term protection by the induction of host innate and adaptive immune responses. In this study, we sought to verify an attenuation strategy by generating 3 double open reading frame (ORF)-deficient recombinant SARS-CoV-2s (rSARS-CoV-2s) simultaneously lacking two accessory ORF proteins (ORF3a\/ORF6, ORF3a\/ORF7a, and ORF3a\/ORF7b). We report that these double ORF-deficient rSARS-CoV-2s have slower replication kinetics and reduced fitness in cultured cells compared with their parental wild-type (WT) counterpart. Importantly, these double ORF-deficient rSARS-CoV-2s showed attenuation in both K18 hACE2 transgenic mice and golden Syrian hamsters. A single intranasal dose vaccination induced high levels of neutralizing antibodies against SARS-CoV-2 and some variants of concern and activated viral component-specific T cell responses. Notably, double ORF-deficient rSARS-CoV-2s were able to protect, as determined by the inhibition of viral replication, shedding, and transmission, against challenge with SARS-CoV-2 in both K18 hACE2 mice and golden Syrian hamsters. Collectively, our results demonstrate the feasibility of implementing the double ORF-deficient strategy to develop safe, immunogenic, and protective LAVs to prevent SARS-CoV-2 infection and associated COVID-19. IMPORTANCE Live-attenuated vaccines (LAVs) are able to induce robust immune responses, including both humoral and cellular immunity, representing a very promising option to provide broad and long-term immunity. To develop LAVs for SARS-CoV-2, we engineered attenuated recombinant SARS-CoV-2 (rSARS-CoV-2) that simultaneously lacks the viral open reading frame 3a (ORF3a) in combination with either ORF6, ORF7a, or ORF7b (\u03943a\/\u03946, \u03943a\/\u03947a, and \u03943a\/\u03947b, respectively) proteins. Among them, the rSARS-CoV-2 \u03943a\/\u03947b was completely attenuated and able to provide 100% protection against an otherwise lethal challenge in K18 hACE2 transgenic mice. Moreover, the rSARS-CoV-2 \u03943a\/\u03947b conferred protection against viral transmission between golden Syrian hamsters.\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-coronavirus-development-of-inactivated-and-live-attenuated-vaccines-publications-lop\u0022 id=pager-heading\u003E\n    \u003Ch3 id=\u0022pagination-for-coronavirus-development-of-inactivated-and-live-attenuated-vaccines-publications-lop\u0022 class=\u0022visually-hidden\u0022\u003Epagination for coronavirus development of inactivated and live attenuated vaccines 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\u003ECoronavirus - Development of inactivated and live-attenuated vaccines Publications LOP\u003C\/span\u003E\n            1 of 2\n          \u003C\/span\u003E      \u003C\/li\u003E\n              \u003Cli\u003E\n          \u003Ca href=\u0022\/lms-lab\/refresh-widget-content\/2926?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}]