Horizontal transmission of a human rotavirus vaccine strain--a randomized, placebo-controlled study in twins.

a b s t r a c t Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts. This randomized (1:1), double-blind study evaluated the potential for transmission of human rotavirus vaccine strain, HRV (RotarixTM) from vaccine recipients to unvaccinated close contacts (twins). 100 pairs of healthy twins aged 6-14 weeks at the time of Dose 1 of HRV vac- cine/placebo were enrolled and one randomly selected twin from each pair received two vaccine doses and the other received placebo doses (at 2 and 4 months of age). Presence of vaccine strain in the stool sam- ples of placebo recipients was an indicator of transmission. Serial stool samples were tested for rotavirus using ELISA at pre-determined time points; rotavirus positive stool samples were tested with RT-PCR and reverse hybridization assay to identify G1P(8) vaccine strain. If G1P(8) vaccine strain was detected, the complete genome was sequenced to assess the similarity between viral isolates. Immunogenicity and safety of HRV vaccine in transmission cases was assessed. 15 transmission cases were reported in 80 evaluable twins who received placebo and the transmission rate was 18.8% (95% CI: 10.9-29.0%). None of the transmission cases was associated with gastroenteritis symptoms. Anti-rotavirus IgA seroconversion was 62.5% (95% CI: 51.0-73.1%) (HRV) and 21.3% (95% CI: 12.9-31.8%) (placebo) 7-weeks post-Dose 2; seroconversion in transmission cases was 26.7% (95% CI: 7.8-55.1%). Genetic variations or amino acid substitutions in transmission cases were similar to that seen in corresponding vaccine recipients. Trans- mission of HRV vaccine strain to unvaccinated twins living in close contact occurred, however, they were not associated with increased of gastroenteritis. Whether transmission leads to indirect protection among unvaccinated individuals remains unknown at this stage.