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.

Purification and propagation of RV from clinical fecal specimen in cell culture is difficult and adaptation to growth in continuous cell lines at high titers usually requires multiple rounds of passaging in primary cells [30] . Consequently, the results of adaptation usually include alterations in the amino acid sequences of the proteins of immunogenic interest. We solved this problem by using a synthetic and codon-optimized DNA cassette, which maintained the original (RV strain Wa, Dhaka isolate) amino acid sequences of the three major capsid proteins VP2, VP6, and VP7. The particular strengths of this approach are three-fold: (1) the vaccine can easily be adjusted to the circulating RV strain, since only the packaged DNA sequence needs to be modified; (2) HSV-1 amplicon vectors have a high transgene capacity (up to 150 kb) that ensures that multiple copies of the RV protein encoding genes are delivered and thereby trigger a high amount of protein synthesis; and (3) VLP purification, which is very expensive and time consuming, can be omitted because VLPs are being formed in situ.