A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever

A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever David Hawman, Shanna Leventhal, Kimberly Meade-White, Amit Khandhar, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3835275/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 May, 2024 Read the published version in npj Vaccines → Version 1 posted 11 You are reading this latest preprint version Abstract Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of Crimean-Congo hemorrhagic fever virus (CCHFV) and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely available vaccines and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Here we evaluate a promising replicating RNA vaccine in a rhesus macaque (Macaca mulatta) model of CCHF. This model provides an alternative to the established cynomolgus macaque model and recapitulates mild-to-moderate human disease. Rhesus macaques infected with CCHFV consistently exhibit viremia, detectable viral RNA in a multitude of tissues and moderate pathology in the liver and spleen. We used this model to evaluate the immunogenicity and protective efficacy of a replicating RNA vaccine. Rhesus macaques vaccinated with RNAs expressing the CCHFV nucleoprotein and glycoprotein precursor developed robust non-neutralizing humoral immunity against the CCHFV nucleoprotein and had significant protection against CCHFV challenge. Together our data report a model of CCHF using rhesus macaques and demonstrate that our replicating RNA vaccine is immunogenic and protective in non-human primates after a prime-boost immunization. Biological sciences/Microbiology/Vaccines/RNA vaccines Biological sciences/Microbiology/Virology Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations There is a conflict of interest J.E. has equity interest in HDT Bio, is a consultant for InBios and is a co-inventor on U.S. patent application no. 62/993,307 “Compositions and methods for delivery of RNA” pertaining to formulations for RNA delivery. DWH, JE and HF are inventors on U.S. patent application number 63/365,015 “Replicating RNA vaccine for Crimean-Congo hemorrhagic fever virus” regarding the repRNA for use against CCHFV. Supplementary Files SupplementalTable1.xlsx SupplementalTable2.xlsx SupplementalTable3.xlsx SupplementalTable4.xlsx supp1.png Supplemental Figure 1: H&E and IHC sections of CCHF20 Cite Share Download PDF Status: Published Journal Publication published 20 May, 2024 Read the published version in npj Vaccines → Version 1 posted Editorial decision: revise 21 Feb, 2024 Review # 1 received at journal 18 Feb, 2024 Review # 3 received at journal 10 Feb, 2024 Review # 2 received at journal 08 Feb, 2024 Reviewer # 3 agreed at journal 31 Jan, 2024 Reviewer # 2 agreed at journal 28 Jan, 2024 Reviewer # 1 agreed at journal 28 Jan, 2024 Reviewers invited by journal 27 Jan, 2024 Editor assigned by journal 15 Jan, 2024 Submission checks completed at journal 08 Jan, 2024 First submitted to journal 04 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3835275","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":269656924,"identity":"7c36373a-d72e-4405-aed2-1160f733180d","order_by":0,"name":"David Hawman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYBACeyA+wMNwAML7wCCRQFCLYQOSFsYZxGgxACmGaWHmYWAgQsvxM4YH3jDckTe4dvjZY9sdFnkM/IuPSeDVcibH4OAchmeGG26nmRvnnpEoZpB4loZfy4G0hMM8DIcZt91OMJPObZNIbJA4Y2yAV8v5Z2At9ttup3+TtiRKy43kAyAtidtu55hJM4K08PcYPsCnxXDG4wMH5xgcTt5/O6dMsheopU2CLRGvFnv+xOYPbyoO286cnb5N4mdbXWI//+EDB/BpgToPic1GRGyiA34i7BgFo2AUjIIRBQCa01LwRKf+PgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-8233-8176","institution":"National Institute of Allergy and Infectious Diseases","correspondingAuthor":true,"prefix":"","firstName":"David","middleName":"","lastName":"Hawman","suffix":""},{"id":269656925,"identity":"8fee64e1-3105-49d9-aedd-c91467094a0f","order_by":1,"name":"Shanna Leventhal","email":"","orcid":"","institution":"National Institute of Allergy and Infectious Diseases","correspondingAuthor":false,"prefix":"","firstName":"Shanna","middleName":"","lastName":"Leventhal","suffix":""},{"id":269656926,"identity":"f74faf94-037c-463d-961a-6d2864ec9332","order_by":2,"name":"Kimberly Meade-White","email":"","orcid":"","institution":"National Institute of Allergy and Infectious Diseases","correspondingAuthor":false,"prefix":"","firstName":"Kimberly","middleName":"","lastName":"Meade-White","suffix":""},{"id":269656927,"identity":"255cbc5e-2f5c-4740-af4b-d62d611d2c72","order_by":3,"name":"Amit Khandhar","email":"","orcid":"","institution":"HDT Bio","correspondingAuthor":false,"prefix":"","firstName":"Amit","middleName":"","lastName":"Khandhar","suffix":""},{"id":269656928,"identity":"b852ca35-91e9-4571-b324-6781a86ab1bd","order_by":4,"name":"Justin Murray","email":"","orcid":"","institution":"National Institute of Allergy and Infectious Diseases","correspondingAuthor":false,"prefix":"","firstName":"Justin","middleName":"","lastName":"Murray","suffix":""},{"id":269656929,"identity":"af6de0fc-5eea-4420-b2a8-1706424c1cf3","order_by":5,"name":"Jamie Lovaglio","email":"","orcid":"https://orcid.org/0000-0002-7567-446X","institution":"NIAID/NIH","correspondingAuthor":false,"prefix":"","firstName":"Jamie","middleName":"","lastName":"Lovaglio","suffix":""},{"id":269656930,"identity":"820e7f51-0569-4fbc-921e-8998006ac1cd","order_by":6,"name":"Carl Shaia","email":"","orcid":"https://orcid.org/0000-0001-8907-8821","institution":"Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health","correspondingAuthor":false,"prefix":"","firstName":"Carl","middleName":"","lastName":"Shaia","suffix":""},{"id":269656931,"identity":"19dccc98-f0c0-4bae-be00-ecfe01ddbbe9","order_by":7,"name":"Greg Saturday","email":"","orcid":"https://orcid.org/0000-0002-0803-6177","institution":"National Institute of Allergy and Infectious Diseases","correspondingAuthor":false,"prefix":"","firstName":"Greg","middleName":"","lastName":"Saturday","suffix":""},{"id":269656932,"identity":"efa2b31f-e2e5-420a-9362-8c2dd00d195d","order_by":8,"name":"Jesse Erasmus","email":"","orcid":"","institution":"HDT Bio Corp","correspondingAuthor":false,"prefix":"","firstName":"Jesse","middleName":"","lastName":"Erasmus","suffix":""},{"id":269656933,"identity":"1d1306d3-6f24-4c93-b5ff-cecbd057436d","order_by":9,"name":"Heinz Feldmann","email":"","orcid":"https://orcid.org/0000-0001-9448-8227","institution":"Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health","correspondingAuthor":false,"prefix":"","firstName":"Heinz","middleName":"","lastName":"Feldmann","suffix":""}],"badges":[],"createdAt":"2024-01-04 20:05:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3835275/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3835275/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41541-024-00887-z","type":"published","date":"2024-05-20T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50344953,"identity":"37ac85f8-2c02-4582-9c17-2a255d439ff7","added_by":"auto","created_at":"2024-01-30 06:14:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":469330,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCMP-CCHFV causes mild-to-moderate disease in RM. \u003c/strong\u003eRhesus macaques were infected with 105TCID50 of CMP-CCHFV via the combined IV and SQ routes. Viral RNA (A) and platelet count in the blood (B) was quantified along with serum AST levels (C). Two animals that showed the highest viremia, greatest decrease in platelets and highest AST levels were euthanized on day 14 for evaluation of viral RNA loads in several tissues (D). The remaining animals were released from the study and no further samples collected.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/11da7f41b1945e52ad17a9b9.png"},{"id":50345606,"identity":"5ffa376e-c7c6-4ac0-a4e1-42b09c0375fd","added_by":"auto","created_at":"2024-01-30 06:22:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":498737,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003erepNP + repGPC is immunogenic in RM. \u003c/strong\u003eGroups of RM were sham vaccinated or vaccinated with repNP + repGPC. CCHFV-specific IgG to whole virus antigen was measured at indicated day post-prime vaccination (DPV) (A – C). (C) is data from (B) but shown at a single dilution to convey the kinetics of the antibody response. (D) IgG responses to specific recombinant antigens was measured by ELISA. (E) An IFNγ ELISpot was performed to measure CCHFV-specific responses to peptides spanning the GPC (G1-14) or NP (N1 – 5). (D) Statistics calculated with a two-way ANOVA with Sidak’s multiple comparisons test. ns P \u0026gt; 0.05, **** P \u0026lt; 0.0001.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/95164c13b604e8b007d16cd1.png"},{"id":50344952,"identity":"22c1c575-6be3-4379-ae7e-8f1d74236d07","added_by":"auto","created_at":"2024-01-30 06:14:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1590790,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProtection in RM correlates with CCHFV-specific IgG. \u003c/strong\u003eEndpoint titers in RM vaccinated with repNP + repGPC were determined (A) and correlation between endpoint titer and viral RNA load in indicated tissues was evaluated (B). Viral RNA in the blood (C), nasal swabs (D) and tissues (E) was quantified by RT-qPCR. Platelet count (F) and AST levels (G) are shown. (H) Anamnestic immune responses against recombinant NP, Gn and Gc were measured on day 7. The Day 0 data is duplicated from figure 2 and included for comparison. (C - E) Statistics calculated with a two-way ANOVA with Tukey’s multiple comparisons test. “*” is comparison of high-titer to sham, “#” is comparison of high to low titer. * P \u0026lt; 0.05, ** P \u0026lt; 0.01, *** P \u0026lt; 0.001, **** P \u0026lt; 0.0001.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/866081632df0d8cfd7a3d009.png"},{"id":50344688,"identity":"5695b734-6906-451c-9f7e-2d6a234de68f","added_by":"auto","created_at":"2024-01-30 06:06:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4397310,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVaccination protects against pathology and viral replication in the liver and spleen. \u003c/strong\u003e(A)\u003cstrong\u003e \u003c/strong\u003eRepresentative images for H\u0026amp;E and IHC for CCHFV NP antigen in the liver, spleen and adrenal gland of sham and repNP + repGPC animals is shown. (B) Scores for presence of antigen as measured by IHC are shown. 0 = none, 1 = rare/few, 2 = scattered, 3 = moderate, 4 = numerous and 5 = diffuse. Statistics calculated with Welch’s t-test. * P \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/acf813041349808dc4566f8a.png"},{"id":56842221,"identity":"cd84abb3-09c5-4bab-9be6-6500fb305292","added_by":"auto","created_at":"2024-05-21 07:10:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2130326,"visible":true,"origin":"","legend":"","description":"","filename":"RepRNAProtectsNHPs.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1_covered_72ee43ad-007f-4b6f-9a37-e5c1fb551921.pdf"},{"id":50344682,"identity":"53c4e095-f27a-4e1d-bc31-2226ca596651","added_by":"auto","created_at":"2024-01-30 06:06:01","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":27073,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/5c7e6c9cf54263aeaa8314ae.xlsx"},{"id":50344685,"identity":"487b4b64-3c39-462a-b501-fd9a4ca1baab","added_by":"auto","created_at":"2024-01-30 06:06:01","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":58921,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/12d1356c04332d8f22ce4a98.xlsx"},{"id":50344690,"identity":"c158568b-be30-43cb-b624-9138a10b59e2","added_by":"auto","created_at":"2024-01-30 06:06:01","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":74305,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"SupplementalTable3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/1417eb595682b2aa2883c941.xlsx"},{"id":50344683,"identity":"ec1fec03-2bcb-4788-a5f7-c3fc112cb6c6","added_by":"auto","created_at":"2024-01-30 06:06:01","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":18555,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/a1162e93e3067311084c86bd.xlsx"},{"id":50344689,"identity":"e9e192f2-e23f-48e8-b8c6-ac6aae6bd2c2","added_by":"auto","created_at":"2024-01-30 06:06:01","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":4680518,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Figure 1: H\u0026amp;E and IHC sections of CCHF20\u003c/p\u003e","description":"","filename":"supp1.png","url":"https://assets-eu.researchsquare.com/files/rs-3835275/v1/f6e18a4c89b4c93690fb24d4.png"}],"financialInterests":"There is a conflict of interest\nJ.E. has equity interest in HDT Bio, is a consultant for InBios and is a co-inventor on U.S. patent application no. 62/993,307 “Compositions and methods for delivery of RNA” pertaining to formulations for RNA delivery. DWH, JE and HF are inventors on U.S. patent application number 63/365,015 “Replicating RNA vaccine for Crimean-Congo hemorrhagic fever virus” regarding the repRNA for use against CCHFV.","formattedTitle":"A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"npj-vaccines","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjvaccines","sideBox":"Learn more about [npj Vaccines](http://www.nature.com/npjvaccines/)","snPcode":"41541","submissionUrl":"https://submission.springernature.com/new-submission/41541/3?","title":"npj Vaccines","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3835275/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3835275/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of Crimean-Congo hemorrhagic fever virus (CCHFV) and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely available vaccines and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Here we evaluate a promising replicating RNA vaccine in a rhesus macaque (Macaca mulatta) model of CCHF. This model provides an alternative to the established cynomolgus macaque model and recapitulates mild-to-moderate human disease. Rhesus macaques infected with CCHFV consistently exhibit viremia, detectable viral RNA in a multitude of tissues and moderate pathology in the liver and spleen. We used this model to evaluate the immunogenicity and protective efficacy of a replicating RNA vaccine. Rhesus macaques vaccinated with RNAs expressing the CCHFV nucleoprotein and glycoprotein precursor developed robust non-neutralizing humoral immunity against the CCHFV nucleoprotein and had significant protection against CCHFV challenge. Together our data report a model of CCHF using rhesus macaques and demonstrate that our replicating RNA vaccine is immunogenic and protective in non-human primates after a prime-boost immunization.","manuscriptTitle":"A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-30 06:05:56","doi":"10.21203/rs.3.rs-3835275/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-02-21T09:07:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-19T04:22:51+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-10T07:03:43+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-09T04:10:21+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-01-31T20:08:30+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-01-29T01:03:06+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-01-28T16:19:00+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-01-28T00:49:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-15T16:39:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-08T07:17:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"npj Vaccines","date":"2024-01-04T20:02:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"npj-vaccines","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjvaccines","sideBox":"Learn more about [npj Vaccines](http://www.nature.com/npjvaccines/)","snPcode":"41541","submissionUrl":"https://submission.springernature.com/new-submission/41541/3?","title":"npj Vaccines","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"05ea5fb1-04ee-45cb-89de-d7585c749bdf","owner":[],"postedDate":"January 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":28409075,"name":"Biological sciences/Microbiology/Vaccines/RNA vaccines"},{"id":28409076,"name":"Biological sciences/Microbiology/Virology"}],"tags":[],"updatedAt":"2024-05-21T07:09:52+00:00","versionOfRecord":{"articleIdentity":"rs-3835275","link":"https://doi.org/10.1038/s41541-024-00887-z","journal":{"identity":"npj-vaccines","isVorOnly":false,"title":"npj Vaccines"},"publishedOn":"2024-05-20 04:00:00","publishedOnDateReadable":"May 20th, 2024"},"versionCreatedAt":"2024-01-30 06:05:56","video":"","vorDoi":"10.1038/s41541-024-00887-z","vorDoiUrl":"https://doi.org/10.1038/s41541-024-00887-z","workflowStages":[]},"version":"v1","identity":"rs-3835275","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3835275","identity":"rs-3835275","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}