Page 54 - TBE_Book_V2_2019

Chapter 2b: The molecular and antigenic structure of TBEV

Figure 4: Binding sites of TBEV E-specific mAbs

1
Surface representation of the TBEV sE dimer [PDB code: 1SVB, ] with the location of amino acids involved in binding
sites of neutralizing mAbs. Epitopes are labeled only on one of the two monomers and the mAbs are designated
according to references. 92,95
Color code of E as in Figure 1.
The figure was prepared with PyMOL (Schrödinger LLC).

products in prM-E expressing cells are E – Virus entry and membrane fusion; Antigenic
immature particles of both size classes, but in structure of TBEV and virus neutralization). 54-60
their mature forms (i.e. after prM cleavage) the Importantly, their particulate nature also makes
larger particles are less stable and therefore them an excellent candidate for use as a
seen as a minority compared to the 30 nm recombinant vaccine antigen, as shown by
particles secreted from transfected cells. mouse immunization and challenge experi-
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Apparently, alternative assembly products can ments. In these experiments, the immuno-
be formed by prM-E interactions. The role of genicity of RSPs was compared with soluble E
subviral particles in natural TBEV infections of dimers, E rosettes formed by detergent removal
ticks and/or mammalian hosts remains to be after solubilization of the viral membrane, and
elucidated. whole formalin-inactivated purified TBEV. With
respect to both the extent of antibody induction
The E protein in RSPs appears to be structurally and protection from challenge, the RSPs were
and functionally identical to that at the surface equivalent to the inactivated virus vaccine. This
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of whole TBE virions. As a consequence, RSPs high immunogenicity is most likely due to the
proved to be a valuable non-infectious model presentation of multiple copies of the native E
systems to assess biological properties of E, protein on a large particulate carrier, mimicking
including membrane fusion and antigenic its presentation on whole virus particles. Similar
structure (see below: Structure and functions of conclusions were also derived from a DNA

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