A recombinant Modified Vaccinia virus Ankara expressing prME of tick-borne encephalitis virus affords mice full protection against TBEV infection

Abstract

IntroductionTick-borne encephalitis virus (TBEV) is an important human pathogen that can cause a serious disease involving the central nervous system (tick-borne encephalitis, TBE). Although approved inactivated vaccines are available, the number of TBE cases is rising, and breakthrough infections in fully vaccinated subjects have been reported in recent years.MethodsIn the present study, we generated and characterized a recombinant Modified Vaccinia virus Ankara (MVA) for the delivery of the pre-membrane (prM) and envelope (E) proteins of TBEV (MVA-prME).ResultsMVA-prME was tested in mice in comparison with a licensed vaccine FSME-IMMUN® and proved to be highly immunogenic and afforded full protection against challenge infection with TBEV.DiscussionOur data indicate that MVA-prME holds promise as an improved next-generation vaccine for the prevention of TBE.

Poor virus-specific T-cell responses early after tick-borne encephalitis virus infection correlate with disease severity

“…Upon infection with TBEV, stronger antibody responses to the E and NS1 proteins are induced than after vaccination [ 2 , 32 ]. We recently showed in mice that antibodies against TBEV E and NS1 proteins afford full or partial protection [ 13 , 18 ]. In the present study, we determined virus-specific IgG, IgM levels and antibody responses to the EDIII and NS1 protein and their neutralizing activity in view of disease severity and outcome.…”

Immunity to Tick-Borne Encephalitis Virus NS3 Protein Induced with a Recombinant Modified Vaccinia Virus Ankara Fails to Afford Mice Protection against TBEV Infection

“…Primary CEF cells (prepared from 10–11-day-old chicken embryos (specific pathogen-free eggs from VALO BioMedia GmbH, Osterholz-Scharmbeck, Germany)), HeLa cells and A549 cells were cultured as described previously [ 35 ]. Wildtype MVA (MVA F6 isolate) and recombinant MVA-GFP (containing green fluorescent protein (GFP) gene in deletion site III under transcriptional control of the late promotor P11 of vaccinia virus (VACV)) [ 37 ] were used.…”

“…Recombinant MVA with integrated NS3 sequence in deletion site III (MVA-NS3) was generated by homologous and intragenomic homologous recombination using the modified standard protocol [ 37 ] ( Figure 1 A). MVA-NS3 was propagated in primary CEF cells and concentrated as described previously [ 35 , 36 ].…”

“…To confirm the correct insertion of the NS3 gene into deletion site III, PCRs specific to the six major deletion sites within the MVA genome were performed according to a slightly modified standard protocol [ 37 ] and as described previously [ 35 , 36 ]. The identity of the insert was confirmed by Sanger sequencing (Microsynth AG, Balgach, Switzerland).…”

“…Recently, we constructed and tested recombinant MVA candidate vaccines expressing the prM-E and NS1 TBEV proteins, respectively. With these recombinant MVAs, we were able to induce E- and NS1-specific antibody and T cell responses which afforded complete or partial protection, respectively, against lethal challenge infection in mice [ 35 , 36 ].…”