The Development Of Multivalent Bovine Rotavirus (Strain Wc3) Reassortant

Abstract

Laboratory and clinical studies have been directed toward development of a vaccine against rotavirus gastroenteritis in infants. First, bovine rotavirus strain WC3, which did not induce neutralizing antibodies to predominant human rotavirus (HRV) serotypes, was determined to be safe and immunogenic; however, it was not protective in all efficacy trials. HRVs adapted to cell culture retained some virulence for infants, but when further attenuated by cold adaptation, they were poorly immunogenic. Reassortant rotaviruses were designed to express HRV surface proteins VP7 (G) or VP4 (P) while retaining a bovine WC3 genome background. Reassortants containing either HRV surface protein and as few as four bovine rotavirus genes were safe in infants. A monovalent WC3 reassortant of serotype G1 specificity was 64%-100% protective in placebo-controlled trials. A quadrivalent WC3 reassortant vaccine with components of HRV G1, G2, G3, and P[8] specificity induced 67% protection against all rotavirus disease in a multicenter efficacy trial.

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges

“…In contrast, in clinical trials in which WC3 was protective, an immune correlate of protection was not identified. 70 Moreover, correlations with protection were also not found in early studies with various WC3/HRV reassortants. 70 In at least 3 very large studies with RV5 in different settings the rates of serum RV-NA and protection have been determined simultaneously; in most cases protection against disease has exceeded the seroresponse rate.…”

“…70 Moreover, correlations with protection were also not found in early studies with various WC3/HRV reassortants. 70 In at least 3 very large studies with RV5 in different settings the rates of serum RV-NA and protection have been determined simultaneously; in most cases protection against disease has exceeded the seroresponse rate. 67,[71][72][73] No statistical analysis of serum RV-NA as a CoP in these studies has been presented.…”

Molecular epidemiology of human P[8],G9 rotaviruses in Hungary between 1998 and 2001

“…In 1999, however, due to a rare association between vaccine use and severe bowel obstruction in vaccinees, the vaccine was withdrawn from the US market (CDC, 1999a, b). Despite these serious adverse effects of vaccination with RotaShield, further efforts at finding safe and effective vaccines are under way (Clark et al, 1996;Bernstein et al, 1998;Clements-Mann et al, 2001).…”

Rotavirus Infection: A Perspective on Epidemiology, Genomic Diversity and Vaccine Strategies

“…This is a vaccine similar to RIT 4237 in that it was derived from a G6 serotype bovine strain (P type 5) that was isolated from a calf with diarrhea in Pennsylvania [21]. The vaccine underwent 12 cell-culture passages prior to evaluation in two efficacy trials.…”

“…RotaTeq (RV5) is a pentavalent vaccine with five separate reassortant viruses, each one that incorporates either a VP7 (G1, G2, G3, G4) or VP4 (P8) gene from a human rotavirus strain on the RNA backbone of the previously discussed WC3 bovine rotavirus strain [21]. Thus, the naturally attenuated WC3 bovine virus was altered to provide crossprotection against epidemiologically important human rotavirus strains.…”