Polyclonal alpaca antibodies protect against hantavirus pulmonary syndrome in a lethal Syrian hamster model.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
31 08 2021
Historique:
received: 11 06 2021
accepted: 11 08 2021
entrez: 1 9 2021
pubmed: 2 9 2021
medline: 9 11 2021
Statut: epublish

Résumé

The use of antibody-based therapies for the treatment of high consequence viral pathogens has gained interest over the last fifteen years. Here, we sought to evaluate the use of unique camelid-based IgG antibodies to prevent lethal hantavirus pulmonary syndrome (HPS) in Syrian hamsters. Using purified, polyclonal IgG antibodies generated in DNA-immunized alpacas, we demonstrate that post-exposure treatments reduced viral burdens and organ-specific pathology associated with lethal HPS. Antibody treated animals did not exhibit signs of disease and were completely protected. The unique structures and properties, particularly the reduced size, distinct paratope formation and increased solubility of camelid antibodies, in combination with this study support further pre-clinical evaluation of heavy-chain only antibodies for treatment of severe respiratory diseases, including HPS.

Identifiants

pubmed: 34465819
doi: 10.1038/s41598-021-96884-6
pii: 10.1038/s41598-021-96884-6
pmc: PMC8408274
doi:

Substances chimiques

Antibodies, Viral 0
Glycoproteins 0
Immunoglobulin G 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17440

Informations de copyright

© 2021. The Author(s).

Références

Kabwe, E. et al. Orthohantaviruses, emerging zoonotic pathogens. Pathogens 9, 1–21 (2020).
doi: 10.3390/pathogens9090775
Abudurexiti, A. et al. Taxonomy of the order Bunyavirales: Update 2019. Arch. Virol. 164, 1949–1965 (2019).
pubmed: 31065850 pmcid: 6641860 doi: 10.1007/s00705-019-04253-6
Jonsson, C. B., Figueiredo, L. T. M. & Vapalahti, O. A global perspective on hantavirus ecology, epidemiology, and disease. Clin. Microbiol. Rev. 23, 412–441 (2010).
pubmed: 20375360 pmcid: 2863364 doi: 10.1128/CMR.00062-09
Avšič-Županc, T., Saksida, A. & Korva, M. Hantavirus infections. Clin. Microbiol. Infect. 21, e6–e16 (2019).
doi: 10.1111/1469-0691.12291
Brocato, R. L. & Hooper, J. W. Progress on the prevention and treatment of hantavirus disease. Viruses 11, 610 (2019).
pmcid: 6669544 doi: 10.3390/v11070610
Liu, R. et al. Vaccines and therapeutics against hantaviruses. Front. Microbiol. 10, 2989 (2020).
pubmed: 32082263 pmcid: 7002362 doi: 10.3389/fmicb.2019.02989
Duchin, J. S. et al. Hantavirus Pulmonary syndrome: A clinical description of 17 patients with a newly recognized disease. N. Engl. J. Med. 330, 949–955 (1994).
pubmed: 8121458 doi: 10.1056/NEJM199404073301401
Safronetz, D., Ebihara, H., Feldmann, H. & Hooper, J. W. The Syrian hamster model of hantavirus pulmonary syndrome. Antiviral Res. 95, 282–292 (2012).
pubmed: 22705798 pmcid: 3425723 doi: 10.1016/j.antiviral.2012.06.002
Mertz, G., Miedzinski, L., Goade, D., Pavia, A. & Hjelle, B. Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America. Clin. Infect. Dis. 39, 1307–1313 (2004).
pubmed: 15494907 doi: 10.1086/425007
Chapman, L., Mertz, G., Peters, C., Jolson, H. & Khan, A. Intravenous ribavirin for hantavirus pulmonary syndrome: Safety and tolerance during 1 year of open-label experience Ribavirin study group. Antivir. Ther. 4, 211–219 (1999).
pubmed: 10723500 doi: 10.1177/135965359900400404
Dibo, M. et al. Antibody therapy for the control of viral diseases: An update. Curr. Pharm. Biotechnol. 20, 1108–1121 (2019).
pubmed: 31400263 doi: 10.2174/1389201020666190809112704
Ter Meulen, J. Monoclonal antibodies for prophylaxis and therapy of infectious diseases. Expert Opin. Emerg. Drugs 12, 525–540 (2007).
pubmed: 17979597 doi: 10.1517/14728214.12.4.525
Bharadwaj, M., Nofchissey, R., Goade, D., Koster, F. & Hjelle, B. Humoral immune responses in the hantavirus cardiopulmonary syndrome. J. Infect. Dis. 182, 43–48 (2000).
pubmed: 10882580 doi: 10.1086/315657
Haese, N. et al. Antiviral biologic produced in DNA vaccine/goose platform protects hamsters against hantavirus pulmonary syndrome when administered post-exposure. PLoS Negl. Trop. Dis. 9, e0003803 (2015).
pubmed: 26046641 pmcid: 4457835 doi: 10.1371/journal.pntd.0003803
Brocato, R., Josleyn, M., Ballantyne, J., Vial, P. & Hooper, J. W. DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS). PLoS ONE 7, e35996 (2012).
pubmed: 22558299 pmcid: 3338771 doi: 10.1371/journal.pone.0035996
Hooper, J. W. et al. DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome. Sci. Transl. Med. 6, 264ra162 (2014).
pubmed: 25429055 doi: 10.1126/scitranslmed.3010082
Perley, C. C. et al. Anti-HFRS human IgG produced in transchromosomic bovines has potent hantavirus neutralizing activity and is protective in animal models. Front. Microbiol. 11, 832 (2020).
pubmed: 32508764 pmcid: 7252588 doi: 10.3389/fmicb.2020.00832
Abbas, A. T., El-Kafrawy, S. A., Sohrab, S. S. & Azhar, E. I. A. IgY antibodies for the immunoprophylaxis and therapy of respiratory infections. Hum. Vaccin. Immunother. 15, 264–275 (2019).
pubmed: 30230944 doi: 10.1080/21645515.2018.1514224
Matsushita, H. et al. Species-specific chromosome engineering greatly improves fully human polyclonal antibody production profile in cattle. PLoS ONE 10, e0130699 (2015).
pubmed: 26107496 pmcid: 4479556 doi: 10.1371/journal.pone.0130699
Duehr, J. et al. Neutralizing monoclonal antibodies against the Gn and the Gc of the andes virus glycoprotein spike complex protect from virus challenge in a preclinical hamster model. MBio 11, e00028-20 (2020).
pubmed: 32209676 pmcid: 7157512 doi: 10.1128/mBio.00028-20
Garrido, J. L. et al. Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo. Sci. Transl. Med. 10, (2018).
Harmsen, M. M. & De Haard, H. J. Properties, production, and applications of camelid single-domain antibody fragments. Appl. Microbiol. Biotechnol. 77, 13–22 (2007).
pubmed: 17704915 pmcid: 2039825 doi: 10.1007/s00253-007-1142-2
Saerens, D. & Muyldermans, S. Overview of Single Domain Antibodies. in Single Domain Antibodies Methods and Protocols 1–573 (2012).
Muyldermans, S. et al. Camelid immunoglobulins and nanobody technology. Vet. Immunol. Immunopathol. 128, 178–183 (2009).
pubmed: 19026455 doi: 10.1016/j.vetimm.2008.10.299
Muyldermans, S. Nanobodies: Natural single-domain antibodies. Annu. Rev. Biochem. 82, 775–797 (2013).
pubmed: 23495938 doi: 10.1146/annurev-biochem-063011-092449
Hamers-Casterman, C. et al. Naturally occurring antibodies devoid of light chains. Nature 363, 446–448 (1993).
pubmed: 8502296 doi: 10.1038/363446a0
Laustsen, A. H. et al. Pros and cons of different therapeutic antibody formats for recombinant antivenom development. Toxicon 146, 151–175 (2018).
pubmed: 29534892 doi: 10.1016/j.toxicon.2018.03.004
Maass, D. R., Sepulveda, J., Pernthaner, A. & Shoemaker, C. B. Alpaca (Lama pacos) as a convenient source of recombinant camelid heavy chain antibodies (VHHs). J. Immunol. Methods 324, 13–25 (2007).
pubmed: 17568607 pmcid: 2014515 doi: 10.1016/j.jim.2007.04.008
Daley, L. P. et al. Effector functions of camelid heavy-chain antibodies in immunity to West Nile virus. Clin. Vaccine Immunol. 17, 239–246 (2010).
pubmed: 19955323 doi: 10.1128/CVI.00421-09
Raj, V. S. et al. Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection. Sci. Adv. 4, eaas9667 (2018).
Laursen, N. S. et al. Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin. Science (80-.) 362, 598–602 (2018).
doi: 10.1126/science.aaq0620
Vial, P. A. et al. A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus. Antivir. Ther. 20, 377–386 (2015).
pubmed: 25316807 doi: 10.3851/IMP2875
Thys, B. et al. In vitro antiviral activity of single domain antibody fragments against poliovirus. Antivir. Res. 87, 257–264 (2010).
pubmed: 20566349 doi: 10.1016/j.antiviral.2010.05.012
Fatima, A. et al. Development of VHH antibodies against dengue virus type 2 NS1 and comparison with monoclonal antibodies for use in immunological diagnosis. PLoS ONE 9, e95263 (2014).
pubmed: 24751715 pmcid: 3994031 doi: 10.1371/journal.pone.0095263
Jähnichen, S. et al. CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc. Natl. Acad. Sci. U. S. A. 107, 20565–20570 (2010).
pubmed: 21059953 pmcid: 2996674 doi: 10.1073/pnas.1012865107
Detalle, L. et al. Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection. Antimicrob. Agents Chemother. 60, 6–13 (2016).
pubmed: 26438495 doi: 10.1128/AAC.01802-15
Griffiths, C., Drews, S. J. & Marchant, D. J. Respiratory syncytial virus: Infection, detection, and new options for prevention and treatment. Clin. Microbiol. Rev. 30, 277–319 (2017).
pubmed: 27903593 doi: 10.1128/CMR.00010-16
Schepens, B. et al. Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion. J. Infect. Dis. 204, 1692–1701 (2011).
pubmed: 21998474 doi: 10.1093/infdis/jir622
Hooper, J. W., Larsen, T., Custer, D. M. & Schmaljohn, C. S. A lethal disease model for hantavirus pulmonary syndrome. Virology 289, 6–14 (2001).
pubmed: 11601912 doi: 10.1006/viro.2001.1133
Safronetz, D. et al. Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus. PLoS Pathog. 7, e1002426 (2011).
pubmed: 22194683 pmcid: 3240607 doi: 10.1371/journal.ppat.1002426
Safronetz, D. et al. Adenovirus vectors expressing hantavirus proteins protect hamsters against lethal challenge with Andes virus. J. Virol. 83, 7285–7295 (2009).
pubmed: 19403663 pmcid: 2704762 doi: 10.1128/JVI.00373-09
Hobernik, D. & Bros, M. DNA vaccines-how far from clinical use?. Int. J. Mol. Sci. 19, 3605 (2018).
pmcid: 6274812 doi: 10.3390/ijms19113605
Fridy, P. C. et al. A robust pipeline for rapid production of versatile nanobody repertoires. Nat. Methods 11, 1253–1260 (2014).
pubmed: 25362362 pmcid: 4272012 doi: 10.1038/nmeth.3170
Haddad, M., Soukkarieh, C., Khalaf, H. E. & Abbady, A. Q. Purification of polyclonal IgG specific for Camelid’s antibodies and their recombinant nanobodies. Open Life Sci. 11, 1–9 (2016).
doi: 10.1515/biol-2016-0001
Meissner, J. D., Rowe, J. E., Borucki, M. K. & St. Jeor, S. C. Complete nucleotide sequence of a Chilean hantavirus. Virus Res. 89, 131–143 (2002).
pubmed: 12367756 doi: 10.1016/S0168-1702(02)00129-6
Toro, J. et al. An outbreak of hantavirus pulmonary syndrome, Chile, 1997. Emerg. Infect. Dis. 4, 687–694 (1998).
pubmed: 9866751 pmcid: 2640255 doi: 10.3201/eid0404.980425
Warner, B. M. et al. Differential pathogenesis between andes virus strains CHI-7913 and Chile-9717869 in Syrian hamsters. J. Virol. 95, e00108-21 (2021).
pmcid: 8139648 doi: 10.1128/JVI.00108-21

Auteurs

Patrycja Sroga (P)

Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
National Centre for Foreign Animal Diseases, Canadian Food Inspection Agency, Winnipeg, MB, Canada.

Angela Sloan (A)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Bryce M Warner (BM)

Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Kevin Tierney (K)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Jocelyne Lew (J)

Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.

Guodong Liu (G)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Michael Chan (M)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Yvon Deschambault (Y)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Derek R Stein (DR)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
Cadham Provincial Laboratory, Winnipeg, MB, Canada.

Geoff Soule (G)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Logan Banadyga (L)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Darryl Falzarano (D)

Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.
Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada.

David Safronetz (D)

Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. david.safronetz@canada.ca.
Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada. david.safronetz@canada.ca.

Articles similaires

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male
Humans Meals Time Factors Female Adult

Classifications MeSH