Safety, Immunogenicity, and Protective Efficacy of One and Three Doses of the Tetravalent Rhesus Rotavirus Vaccine in Infants in Lima, Peru

Abstract

An oral rhesus-human rotavirus tetravalent (RRV-TV) vaccine (10(4) pfu of rhesus rotavirus [type G3] and of 3 human-rhesus reassortants [G1, G2, and G4]) was evaluated in a field trial in Lima, Peru. At 2, 3, and 4 months of age, infants received either a dose of RRV-TV, an initial dose of vaccine followed by a dose of placebo at 3 and 4 months, or a dose of placebo. Rotavirus-specific IgA responses were detected by ELISA in 75% of the three-dose vaccine group, 59% of the one-dose vaccine group (P = .05), and 24% of the placebo group (P < .001): 64%, 48%, and 12% of each group, respectively, had a neutralizing antibody response to at least 1 serotype. Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea; however, they did provide some protection (range, 35%-66%) against more severe rotavirus diarrhea, especially for episodes caused by type G1.

Serum and intestinal isotype antibody responses to Wa human rotavirus in gnotobiotic pigs are modulated by maternal antibodies.

“…Interference by maternal antibodies may explain the need for two or more rotavirus infections (symptomatic or asymptomatic) to provide protection against moderate to severe diarrhoea in Mexican children (Velazquez et al, 1996). Lanata et al (1996) have reported that in Peru, three doses of oral rotavirus vaccine (4i10% p.f.u. per dose) did not increase vaccine efficacy compared with one dose (efficacies of 35-66 % against severe diarrhoea), whereas Perez-Schael et al (1997) found in Venezuela that three doses of 4i10& p.f.u.…”

“…Several oral vaccines have been developed based on heterologous host rotaviruses, attenuated human rotavirus (HRV) and human-animal rotavirus reassortants. A tetravalent human-rhesus reassortant rotavirus vaccine was effective in reducing rotavirus-induced diarrhoea in trials in the USA and Finland (Bernstein et al, 1995 ;Joensuu et al, 1997 ;Rennels et al, 1996 ;Ward et al, 1997) but was less effective in trials in some developing countries (Lanata et al, 1996 ;Linhares et al, 1996). The reduced efficacy may reflect the lower vaccine dose used in these latter trials (4i10% vs 4i10& p.f.u.)…”

“…The reduced efficacy may reflect the lower vaccine dose used in these latter trials (4i10% vs 4i10& p.f.u.) (Perez-Schael et al, 1997), differences in titres of maternal antibodies (Rimer et al, 1992), differences in exposure to rotavirus before and during the vaccination process (Joensuu et al, 1997 ;Lanata et al, 1996 ;Linhares et al, 1996) or differences in trial design (Perez-Schael et al, 1997).…”

“…The reported effect of breast feeding on immune responses to oral vaccination is inconsistent but there is a trend toward lower seroconversion rates in breast-fed infants (Pichichero, 1990 ;Glass et al, 1991 ;Rimer et al, 1992 ;Rennels, 1996). The suppressive effect of maternal antibodies may be more important in developing countries, where lower vaccine efficacies have been observed in vaccine trials in Thailand (Migasena et al, 1995), Peru (Lanata et al, 1996), Brazil (Linhares et al, 1996) and Venezuela (Rimer et al, 1992 ;Vesikari, 1997). Rimer et al (1992) reported higher rotavirus antibody titres in breast milk from Venezuelan mothers than in milk from mothers in New York State and used logistic regression to demonstrate the suppressive effects of both milk and serum antibodies on seroconversion rates following oral rotavirus vaccination.…”

Increased Prevalence of G1P[4] Genotype among Children with Rotavirus-Associated Gastroenteritis in Metropolitan Detroit

“…The first oral RV vaccine (Rotashield) was clinically effective in five global trials (12,15,18,20). However, it was withdrawn because of possible causative relationship to intussusception in infants (14).…”