Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

Meier, Anita F.; Suter, Mark; Schraner, Elisabeth M.; Humbel, Bruno M.; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S.

A rationale of structural vaccinology is to maintain the native three-dimensional structure and to stabilize the conformation of antigens to induce an efficacious immune response. We and others [14, 17, 27, 31] reported that assembly of structural proteins into VLPs might be crucial for protection against RV infections. The viral structure is assembled by several proteins on the VLP surface mimicking the native virions and allowing crucial overlapping epitopes to be recognized by antibodies that would not be possible by the use of single individual subunits as antigens. Adopting these principles, we propose that the structural aspect of RVLPs is important for RV specific generation of protective antibodies. Based on electron microscopic analysis, the RVLPs produced in vitro were highly analogous to native RV particles. However, further analysis revealed that cell culture purified RVLPs were predominantly composed of VP2 and VP6 but excluded VP7 ( Figure 5C ). As known from literature [1, 32] , and shown by our data of the intracellular localization of the synthetized proteins ( Figure 1D ), VP7 associates with the membranes of the ER, whereas VP2 and VP6 form punctate structures within the cytoplasm but do not co-localize with the ER membranes. It is not fully understood how triple-layered particles (TLP) can form under these conditions. However, Coste et al. were able to purify TLPs following co-infection of insect cells with three different baculoviruses [27] (i.e., one for the expression of each of the three capsid proteins, VP2, VP6, and VP7).