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

蜱传脑炎疫苗突破性感染诱导对非结构蛋白产生异常的 T 细胞和抗体反应

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作者:Amare Aregay, Jan Slunečko, Miša Korva, Petra Bogovic, Katarina Resman Rus, Nataša Knap, Jana Beicht, Mareike Kubinski, Giulietta Saletti, Tatjana Avšič-Županc, Imke Steffen #, Franc Strle #, Albert D M E Osterhaus #, Guus F Rimmelzwaan #

Abstract

Tick-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.

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