Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model

Yu, K.-M., Park, S.-J., Yu, M.-A., Kim, Y.-I., Choi, Y., Jung, J. U., Brennan, B. and Choi, Y. K. (2019) Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model. Proceedings of the National Academy of Sciences of the United States of America, 116(52), pp. 26900-26908. (doi: 10.1073/pnas.1914704116) (PMID:31818942) (PMCID:PMC6936527)

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Abstract

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Due to the recent emergence of SFTSV, there has been little time to conduct research into preventative measures aimed at combatting the virus. SFTSV is listed as one of the World Health Organization’s Prioritized Pathogens for research into antiviral therapeutics and vaccine development. Here, we report 2 attenuated recombinant SFTS viruses that induce a humoral immune response in immunized ferrets and confer complete cross-genotype protection to lethal challenge. Animals infected with rHB29NSsP102A or rHB2912aaNSs (both genotype D) had a reduced viral load in both serum and tissues and presented without high fever, thrombocytopenia, or mortality associated with infection. rHB29NSsP102A- or rHB2912aaNSs-immunized animals developed a robust anti-SFTSV immune response against cross-genotype isolates of SFTSV. This immune response was capable of neutralizing live virus in a focus-reduction neutralization test (FRNT) and was 100% protective against a cross-genotype lethal challenge with the CB1/2014 strain of SFTSV (genotype B). Thus, using our midsized, aged ferret infection model, we demonstrate 2 live attenuated vaccine candidates against the emerging pathogen SFTSV.

Item Type:Articles
Additional Information:This work was supported by the Korea Health Technology R and D Project, funded by the Ministry of Health and Welfare, Republic of Korea (HI15C2817); and the Ministry of Health and Welfare Government-wide Research and Development Fund Project for Infectious Disease Research (HG18C0029) (to Y.K.C.). B.B. is supported by Wellcome Trust/Royal Society Sir Henry Dale Fellowship 210462/Z/18/Z and, previously, Wellcome Trust Senior Investigator Award 099220/Z/12/Z (to R. M. Elliott). J.U.J. is supported by NIH Grants AI116585, AI129496, AI40718, and AI140705.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brennan, Dr Benjamin
Authors: Yu, K.-M., Park, S.-J., Yu, M.-A., Kim, Y.-I., Choi, Y., Jung, J. U., Brennan, B., and Choi, Y. K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:09 December 2019
Copyright Holders:Copyright © 2019 the Authors
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 116(52):26900-26908
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301176What makes phleboviruses tick? Examining the molecular interactions of tick-borne phleboviruses with their arthropod vectorBenjamin BrennanWellcome Trust (WELLCOTR)210462/Z/18/ZIII - Centre for Virus Research
168602Molecular analyses of arbovirus-host interactionsAgnes SimpsonWellcome Trust (WELLCOTR)099220/B/12/ZIII-MRC-GU Centre for Virus Research