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

Three phase l trials of the rhesus rotavirus (RRV) based quardrivalent vaccine composed of sero-type 3 (RRV), and serotypes 1 (D × RRV), 2 (DS1 × RRV), and 4 (ST3 × RRV) human rotavirus × 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 × 10⁴PFUeachof D × RRV and RRV, followed 4 weeks later by 1 × 10⁴ PFU each of DS1 × RRV and ST3 × RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10⁴ PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10⁴ 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 (10⁵ PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10⁵ PFU) or 4) two doses of M37 vaccine (10⁵ PFU), or 5) M37 vaccine (10⁵ PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week post-vaccination 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. Neutralization seroresponses to human rotaviruses in infants receiving quadrivalent vaccine ranged from 9% (to serotype 3 in recipients of the first dose of bivalent vaccine in trial I) to 68% (to serotype 1 in recipients of two doses of higher titered quadrivalent vaccine in trial III). M37 vaccine induced homologous neutralization responses in 33-78% of the infants and responses to human strains sharing its VP7 (Wa) or VP4 (ST3) serotype in 13-35% of the infants. Overall, both vaccine candidates induced a greater number of antibody responses when two doses or a higher titered preparation was administered. © 1994 Wiley-Liss, Inc.