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  • Hinkula, JormaLinköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Karolinska Institute, Sweden (författare)

Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • AMER SOC MICROBIOLOGY,2017
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-138278
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-138278URI
  • https://doi.org/10.1128/JVI.02076-16DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135816744URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|European Commission under the Health Cooperation Work Programme [260427]; European Unions Horizon research and innovation program [732732]
  • Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR(- / -)) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is responsible for hemorrhagic diseases in humans, with a high mortality rate. There is no FDAapproved vaccine, and there are still gaps in our knowledge of the immune responses to infection. The recently developed mouse models mimic human CCHF disease and are useful to study the immunogenicity and the protection by vaccine candidates. Our study shows that mice vaccinated with a specific DNA vaccine were fully protected. Importantly, we show that neutralizing antibodies are not sufficient for protection against CCHFV challenge but that an extra Th1-specific cellular response is required. Moreover, we describe the identification of five conserved B-cell epitopes, of which only one was previously known, that could be of great importance for the development of diagnostics tools and the improvement of vaccine candidates.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Devignot, StephaniePhilipps University of Marburg, Germany; Justus Liebig University, Germany (författare)
  • Åkerström, SaraNational Vet Institute, Sweden (författare)
  • Karlberg, HelenFolkhälsomyndigheten, Sweden (författare)
  • Wattrang, EvaNational Vet Institute, Sweden (författare)
  • Bereczky, SandorFolkhalsomyndigheten, Sweden (författare)
  • Mousavi-Jazi, MehrdadFolkhalsomyndigheten, Sweden (författare)
  • Risinger, ChristianDepartment of Chemistry, University of Copenhagen, Frederiksberg, Denmark (författare)
  • Lindegren, GunnelFolkhalsomyndigheten, Sweden (författare)
  • Vernersson, CarolineNational Vet Institute, Sweden (författare)
  • Paweska, JanuszNational Institute Communicable Disease, South Africa (författare)
  • Jansen van Vuren, PetrusNational Institute Communicable Disease, South Africa (författare)
  • Blixt, OlaUniversity of Copenhagen, Denmark (författare)
  • Brun, AlejandroInstitute Nacl Invest and Tecnol Agriculture and Alimentaria, Spain (författare)
  • Weber, FriedemannPhilipps University of Marburg, Germany; Justus Liebig University, Germany (författare)
  • Mirazimi, AliKarolinska Institutet,Folkhälsomyndigheten, Sweden; National Vet Institute, Sweden; Karolinska Institute, Sweden (författare)
  • Linköpings universitetAvdelningen för mikrobiologi och molekylär medicin (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Virology: AMER SOC MICROBIOLOGY91:100022-538X1098-5514

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