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Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses
Örebro universitet, Institutionen för medicinska vetenskaper. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Örebro universitet, Institutionen för medicinska vetenskaper. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
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2019 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Refereegranskat)
Abstract [en]

Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. Chronic infections with the hepatitis C virus (HCV) can be effectively cured by antivirals. However, as cured patients can be re-infected they lack protective immune responses. In addition, the relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect vaccines with high efficiency to control and possibly eradicate Hepatitis viruses globally. The vaccine should induce either, or both, neutralizing antibodies and protective T cell responses. We therefore have developed DNA based flavivirus replicons as a potent delivery system that effectively prime HCV-specific T cell responses. We generated suicidal subgenomic DNA replicons of Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), and Kunjinvirus (KUNV) expressing either a fusion protein between the HCV NS3/4A and a stork hepatitis B virus core or a vaccine candidate gene of HB/DV. Transfection experiments showed that the antigen expression by KUNV and WNV replicons was several folds higher than the antigen expression by standard DNA plasmid with CMV promoter. The immunogenicity of three suicidal flaviviral DNA replicons expressing HCV NS3/4A was tested in mice and compared to HCV NS3/4A expression by the standard DNA plasmid. The KUNV-HCV replicon was the best replicon-based immunogen with respect to priming of HCV NS3/4A-specific T cells as determined by ELISpot, dextramer staining, and polyfunctionality. Importantly, a mutant KUNV-HCV immunogen lacking replication failed to induce immune responses. Thus, the newly developed KUNV-based suicidal DNA launched replicon vaccine for HCV is a highly attractive candidate as a prophylactic vaccine against chronic hepatitis C. In addition, we are currently testing the immunogenicity of KUNV-HB/DV replicon in mice.

Ort, förlag, år, upplaga, sidor
2019.
Nationell ämneskategori
Medicin och hälsovetenskap Immunologi Infektionsmedicin
Forskningsämne
Molekylärbiologi; Infektionssjukdomar; Immunologi
Identifikatorer
URN: urn:nbn:se:oru:diva-76634OAI: oai:DiVA.org:oru-76634DiVA, id: diva2:1353180
Konferens
16th Smögen Summer Symposium on Virology, Smögen, Sweden, August 22-24, 2019
Tillgänglig från: 2019-09-20 Skapad: 2019-09-20 Senast uppdaterad: 2019-09-23Bibliografiskt granskad

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Asghar, NaveedTran, Pham Tue HungMelik, WessamJohansson, Magnus

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Asghar, NaveedTran, Pham Tue HungMelik, WessamJohansson, Magnus
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Institutionen för medicinska vetenskaper
Medicin och hälsovetenskapImmunologiInfektionsmedicin

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