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

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Abstract
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.