Increased Vaccination Diversity Leads to Higher and Less-Variable Neutralization of TBE Viruses of the European Subtype

Abstract

Tick-borne encephalitis (TBE) is an infectious disease of the central nervous system. The causative agent is the tick-borne encephalitis virus (TBEV), which is most commonly transmitted by tick bites, but which may also be transmitted through the consumption of raw dairy products or, in rare instances, via infected transfusions, transplants, or the slaughter of infected animals. The only effective preventive option is active immunization. Currently, two vaccines are available in Europe—Encepur® and FSME-IMMUN®. In Central, Eastern, and Northern Europe, isolated TBEV genotypes belong mainly to the European subtype (TBEV-EU). In this study, we investigated the ability of these two vaccines to induce neutralizing antibodies against a panel of diverse natural TBEV-EU isolates from TBE-endemic areas in southern Germany and in regions of neighboring countries. Sera of 33 donors vaccinated with either FSME-IMMUN®, Encepur®, or a mixture of both were tested against 16 TBEV-EU strains. Phylogenetic analysis of the TBEV-EU genomes revealed substantial genetic diversity and ancestry of the identified 13 genotypic clades. Although all sera were able to neutralize the TBEV-EU strains, there were significant differences among the various vaccination groups. The neutralization assays revealed that the vaccination using the two different vaccine brands significantly increased neutralization titers, decreased intra-serum variance, and reduced the inter-virus variation.

A reporter virus particle seroneutralization assay for tick-borne encephalitis virus overcomes ELISA limitations

“…While there was a strong correlation between RVP-based and virus-based SNT assays when the strain Neudoerfl was used in both assays (R 2 0.86, Figure 1A), TBEV RVP SNT results correlated less well to TBEV WT SNT results using the strain Hypr (R 2 0.55, Supplementary Figure 4), as expected since the TBEV RVP utilized in this study is derived from the genetic sequence of the Neudoerfl strain of TBEV. The results are in line with literature, where it has been shown that antibodies generated upon vaccination with specific strains do not equally efficiently neutralize different wild type virus strains (38, 39).…”