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.

The salient new findings in our study include: (1) transduction of cells with our HSV-1 amplicon vector delivering a DNA cassette encoding a single polycistronic messenger RNA, comprising the codon-optimized sequences of the three RV capsid proteins VP2, VP6, and VP7, triggered the synthesis of all three encoded RV proteins; (2) cell-type dependent increase of the desired protein synthesis due to codon-optimization of the capsid protein coding sequences in the vector; (3) assembly of VP2 and VP6 into double-layered virus-like particles, while VP7 was synthesized in the same cell but, apparently, excluded from particle formation; (4) intramuscular inoculation of these amplicon particles resulted in the production of RV-specific antibodies against VP2 and VP6 but, interestingly, not VP7; (5) these antibodies were transferred to mouse progeny via the uterine and lactogenic pathway; and (6) despite efficient antibody transfer to offspring, clinical protection against diarrhea upon experimental infection of the pups with a heterologous, mouse-specific RV was not achieved.