Development of a Pentavalent Rotavirus Vaccine against Prevalent Serotypes of Rotavirus Gastroenteritis

Abstract

The strategy of decreasing the morbidity and mortality associated with rotavirus gastroenteritis through vaccination is supported by studies demonstrating that wild-type rotavirus infection protects against subsequent rotavirus disease. Primary infection with wild-type rotavirus typically induces homotypic immunity. Vaccination of infants with a multivalent vaccine directed against prevalent rotavirus serotypes is the strategy most likely to provide the broadest degree of protection against rotavirus gastroenteritis. The pentavalent human-bovine reassortant rotavirus vaccine (HBRV) is directed against each of the most prevalent rotavirus serotypes, including G1, G2, G3, G4, and P1. The safety, immunogenicity, and efficacy of different reassortant compositions and formulations of the HBRV have been evaluated in clinical trials. An HBRV dose of > or =8 x 10(6) plaque-forming units has demonstrated 68.8%-76.6% efficacy against any rotavirus gastroenteritis, regardless of severity, and approximatel 100% efficacy against severe rotavirus gastroenteritis for the first rotavirus infection season after vaccination. The HBRV has been generally well tolerated, with no increase in the incidence of fever, vomiting, diarrhea, or behavioral changes among vaccine recipients, compared with placebo recipients, during the 14- and 42-day periods after administration of any dose. Shedding of vaccine strains in feces is uncommon. A large-scale trial is under way to evaluate the efficacy and safety of the manufacturing-scale formulation of pentavalent HBRV.

Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

“…4,22 During routine rotavirus immunization of young children it is likely that mixed schedules of the 2 vaccines are administered to infants. In fact, a recently published study 6 …”

“…A randomized, nonblinded (for the subject and study team), multicenter study was conducted at 6 Eligible subjects were healthy infants (determined by medical history, physical examination, and medical assessment), at least 6 weeks and ≤15 weeks of age at first vaccination. Parents or legal guardians provided signed informed consent.…”

“…A subject was considered to have a seropositive result if the IgA antibody concentration determined using either virus was ≥20 U/mL. 16 Neutralizing antibody was determined against several rotavirus strains representing the common G and P types: Wa(G1P [8]), DS-1(G2P [4]), P(G3P [8]), ST3(G4P [6 ]), VA70(G4P [8]), and CCHMC-G9P6(G9P [6]) by using a method described previously. 17 A subject was considered to have a seropositive result for neutralizing antibody if the titer determined against any virus was ≥10.…”

“…Proportion of Subjects Who Were Seropositive for Serum Neutralizing Rotavirus Antibodies (Titer DS-1 G2P [4] P G3P [8] ST3 G4P [6] VA70 G4P [8] CCHMC-G9P6 G9P [6] n/N by guest on May 11, 2018 http://pediatrics.aappublications.org/ Downloaded from evaluating rotavirus vaccine uptake in private US practices showed that 3% received a combination of the 2 vaccines. 23 However, no data exist, to our knowledge, on the impact of sequential schedules on safety or immunogenicity when compared with administration of a single vaccine type in the recommended schedule.…”

“…4,5 RV5 is a live, oral vaccine that contains a combination of 5 human/ bovine reassortant rotaviruses. 6,7 Three doses of the vaccine are recommended. RV1 is a liveattenuated human rotavirus vaccine prepared from a single human strain (G1P [8]), 8,9 and 2 doses are recommended.…”