Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period

Abstract

Background: Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age.

Methods: In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months.

Results: In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype.

Conclusions: RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

Keywords: Ghana; attenuated; diarrhea; gastroenteritis; humans; infant; infantile; randomized controlled trial; rotavirus; rotavirus infections; rotavirus vaccines; vaccines.

Figure 1.

Flow diagram of the progress through the phases of the trial. [1] Inclusion criteria: Investigator's judgment regarding protocol adherence, aged 0 to 29 days, written parental permission, healthy, birth weight >2000 g or, if birth weight unknown, gestation period >37 weeks. [2] Exclusion criteria: Use or planned use of other investigational drug or vaccine, participation or planned participation in another clinical study of drug or vaccine, plans for nonroutine vaccine within 14 days of rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) or placebo dose, chronic administration of immunosuppressants since birth, clinically significant history of chronic gastrointestinal disease, including any uncorrected congenital malformation of the gastrointestinal tract, intussusception, or other medical condition determined to be serious by the investigator, confirmed or suspected immunosuppressive or immunodeficient condition, history of allergic disease or reaction likely to be exacerbated by any component of the vaccine, acute disease at the time of enrollment. Gastroenteritis (GE) within 7 days, rotavirus gastroenteritis (RV-GE), family history of congenital or hereditary immunodeficiency, receipt of immunoglobulins and/or blood products (except hepatitis B immune globulin [HBIG]), neurologic disorders or seizures, or clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality. [3] Subjects were lost to follow-up rather than from parental withdrawal of consent, treatment failure, investigator opinion , protocol deviations, request of the sponsor, or breaks in the randomization code. [4] Some subjects had more than one major protocol deviation.