Tick-borne encephalitis vaccine breakthrough infections induce aberrant T cell and antibody responses to non-structural proteins

Author:

Aregay AmareORCID,Slunečko Jan,Korva MišaORCID,Bogovic Petra,Resman Rus KatarinaORCID,Knap NatašaORCID,Beicht JanaORCID,Kubinski Mareike,Saletti Giulietta,Avšič-Županc TatjanaORCID,Steffen Imke,Strle Franc,Osterhaus Albert D. M. E.ORCID,Rimmelzwaan Guus F.ORCID

Abstract

AbstractTick-borne encephalitis virus (TBEV) vaccine breakthrough (VBT) infections are not uncommon in endemic areas. The clinical and immunological outcomes have been poorly investigated. We assessed the magnitude and specificity of virus-specific antibody and T cell responses after TBE in previously vaccinated subjects and compared the results with those of unvaccinated TBE patients and study subjects that received vaccination without VBT infection. Symptomatic TBEV infection of unvaccinated study subjects induced virus-specific antibody responses to the E protein and non-structural protein 1 (NS1) as well as T cell responses to structural and other non-structural (NS) proteins. After VBT infections, significantly impaired NS1-specific antibody responses were observed, while the virus-specific T cell responses to the NS proteins were relatively strong. VBT infection caused predominantly moderate to severe disease during hospitalization. The level of TBEV EDIII- and NS1-specific antibodies in unvaccinated convalescent patients inversely correlated with TBE severity and neurological symptoms early after infection.

Funder

Alexander von Humboldt-Stiftung

EC | Horizon 2020 Framework Programme

The Slovenian Research and Innovation Agency

Univerza v Ljubljani

Bundesministerium für Bildung und Forschung

Publisher

Springer Science and Business Media LLC

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