Immunity to Tick-Borne Encephalitis Virus NS3 Protein Induced with a Recombinant Modified Vaccinia Virus Ankara Fails to Afford Mice Protection against TBEV Infection
Mareike Kubinski,
Jana Beicht,
Thomas Gerlach,
Amare Aregay,
Albert D. M. E. Osterhaus,
Alina Tscherne,
Gerd Sutter,
Chittappen Kandiyil Prajeeth,
Guus F. Rimmelzwaan
Affiliations
Mareike Kubinski
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Jana Beicht
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Thomas Gerlach
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Amare Aregay
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Albert D. M. E. Osterhaus
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Alina Tscherne
Division of Virology, Institute for Infectious Diseases and Zoonoses, Ludwig Maximilian University Munich, Sonnenstraße 24, 85764 Oberschleißheim, Germany
Gerd Sutter
Division of Virology, Institute for Infectious Diseases and Zoonoses, Ludwig Maximilian University Munich, Sonnenstraße 24, 85764 Oberschleißheim, Germany
Chittappen Kandiyil Prajeeth
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Guus F. Rimmelzwaan
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
Tick-borne encephalitis (TBE) is a serious neurological disease caused by TBE virus (TBEV). Because antiviral treatment options are not available, vaccination is the key prophylactic measure against TBEV infections. Despite the availability of effective vaccines, cases of vaccination breakthrough infections have been reported. The multienzymatic non-structural protein 3 (NS3) of orthoflaviviruses plays an important role in polyprotein processing and virus replication. In the present study, we evaluated NS3 of TBEV as a potential vaccine target for the induction of protective immunity. To this end, a recombinant modified vaccinia virus Ankara that drives the expression of the TBEV NS3 gene (MVA-NS3) was constructed. MVA-NS3 was used to immunize C57BL/6 mice. It induced NS3-specific immune responses, in particular T cell responses, especially against the helicase domain of NS3. However, MVA-NS3-immunized mice were not protected from subsequent challenge infection with a lethal dose of the TBEV strain Neudoerfl, indicating that in contrast to immunity to prME and NS1, NS3-specific immunity is not an independent correlate of protection against TBEV in this mouse model.
