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

Abstract

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 (Rotarix™) 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 vaccine/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 samples 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. Transmission 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.

Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto, South Africa

“…The horizontal transmission of a human rotavirus vaccine strain -from vaccinated children to their unvaccinated twins -was demonstrated in a placebo-controlled study of twins who lived in close contact with each other in the Dominican Republic. 26 The overall frequency of seroconversion observed in the present study following the second dose of Rotarix ® -61% -is reassuring, bearing in mind that the rotavirus vaccination schedule currently followed in South Africa, of doses at 6 and 14 weeks of age, has not yet been studied in clinical trials. This frequency of seroconversion is similar to the values observed in the South African trial of the clinical efficacy of Rotarix ® , which were 57.1% (95% CI: 44.7-68.9) after two doses and 66.7% (95% CI: 54.0-77.8) after three doses.…”

Use of rotavirus vaccines in preterm babies on the neonatal unit

“…Shedding has been documented up to 15 days postimmunization [16]. In a twin study, 29% of unvaccinated contacts had evidence of seroconversion following vaccination of their twin, but none reported gastroenteritis symptoms [17]. This study, however, is not necessarily transferrable to infants in the neonatal units given that in this study the twins were in a nonclinical environment with no infection control precautions and may not be as susceptible to infection.…”

Rotavirus Vaccination of Very Low Birth Weight Infants at Discharge From the NICU

“…Rivera et al 15 showed that infants who received the human rotavirus vaccine transmitted the vaccine strain to their unvaccinated twin sibling ∼19% of the time, but there was no increased risk of gastroenteritis in this group. This model of transmission may not apply to a NICU setting because the infants in this study were healthy twins, $32 weeks' gestation, and already discharged from the hospital.…”