Safety, efficacy, and immunogenicity of 2 doses of bovine-human (UK) and rhesus-rhesus-human rotavirus reassortant tetravalent vaccines in Finnish children

Background. Live oral rhesus-rhesus-human rotavirus reassortant tetravalent (RRV-TV) vaccine was efficacious against rotavirus gastroenteritis but was withdrawn because of a rare association with intussusception. A corresponding tetravalent (types G1, G2, G3, and G4) reassortant vaccine based on bovine-human (UK) rotavirus reassortant tetravalent (BRV- TV) vaccine was developed concurrently. Methods. Before the withdrawal of RRV-TV vaccine, parallel placebo-controlled trials of BRV- TV vaccine ( observer blinded) versus RRV-TV vaccine (double blinded) with a 2: 1 ratio of vaccine: placebo were conducted in Finland in a total of 510 infants. Two doses of study vaccine or placebo were administered at ages 3 and 5 months. Results. The first dose of RRV-TV vaccine was followed by a significant excess rate of febrile reactions (36%), whereas the rate of fever after the administration of BRV- TV vaccine did not differ significantly from that in the placebo group. Neither vaccine induced diarrhea. A seroresponse was detected in 97% of BRV- TV vaccine recipients and 94% of RRV-TV vaccine recipients. Both vaccines were equally effective, with 68%-69% efficacy against any and 88%-100% efficacy against severe rotavirus gastroenteritis during the first epidemic season. Conclusions. BRV- TV vaccine is a promising new candidate rotavirus vaccine, with low reactogenicity and high efficacy. Two doses of BRV- TV or RRV-TV vaccine are sufficient for the induction of protection against severe rotavirus disease.