Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus‐based quadrivalent and the M37 rotavirus vaccine candidates

Abstract

Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of the Rhesus Rotavirus–Based Quadrivalent Vaccine in Infants and Young Children in Venezuela

“…5,6 The vaccine was safe. As in most previous studies, 5,6,8,9,[37][38][39] however, during the six days after the first dose there were self-limited febrile responses; these occurred in 15 percent of vaccinated infants and 7 percent of placebo recipients in our study. On day 3 after vaccination, 5 percent of the vaccinated infants and 1 percent of the placebo recipients had temperatures of 38.1°C or more.…”

Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E

“…The complete genome sequence of only one asymptomatic neonatal strain, ST3 (G4P[6]), has been reported to date, but partial genome sequences exist for M37 (G1P[6]) and I321 (G10P[11]) (Dunn et al, 1994; Heiman et al, 2008; Kirkwood and Palombo, 1997; Palombo and Bishop, 1994a; Rao et al, 1995). Strains M37 and I321 were originally considered as vaccine candidates, along with RV3 and 116E, prior to studies showing that they are poorly immunogenic or do not protect against RV disease (Bhandari et al, 2006; Perez-Schael et al, 1994; Vesikari et al, 1991). While the evolutionary origin of M37 is unknown, I321 is thought to have derived from an inter-species transmission of a bovine RV to a human, providing a basis for its lack of virulence (Sukumaran et al, 1992).…”

Rotavirus Immunoglobulin A Responses Stimulated by Each of 3 Doses of a Quadrivalent Human/Bovine Reassortant Rotavirus Vaccine

“…In a study conducted in Peru, only 9 (36%) of 25 vaccine recipients examined shed detectable amounts of rotavirus after the first dose of RRV-TV, and this percentage decreased to 24% and 12% after doses 2 and 3, respectively [9]. An even more dramatic effect on virus shedding as a function of dose number was observed after RRV-TV vaccination in Venezuela: virus shedding was detected in 11 (48%) of 23 vaccine recipients after the first dose and in 0 of 20 after the second dose [10]. Interference with viral replication after sequential dosing also was observed after administration of the individual strains contained in the RRV-TV vaccine [11].…”