Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: A randomized, double-blind, placebo controlled trial

Abstract

Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P [8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1,773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre-and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3 -8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3 -14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (Vaccine Efficacy 38.1% (9.8 -57.3). The point estimate of efficacy in the second year of life (17.6%; −59.2 -56.0) was lower than in the first year of life (49.4%; 19.2 -68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who Publisher's Disclaimer: This is the author's version of a work that was accepted for publication in Vaccine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Vaccine 2012;30, Supplement 1(0):A36-A43. Europe PMC Funders Group

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

“…In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC.…”

“…However, there is consistent evidence from clinical trials that RV have lower efficacies in low-and middle-income countries (LMIC): vaccine efficacies are 80 to 90% in high-income countries (HIC) and 40 to 60% in LMIC (3-8). Indeed, there is growing evidence from vaccine effectiveness studies emerging from the field that in real-life use, vaccine effectiveness is also consistently lower in LMIC (9-12).In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC.…”

Characterization and protective efficacy in an animal model of a novel truncated rotavirus VP8 subunit parenteral vaccine candidate

“…In middle-and high-income countries [5][6][7], the two vaccines have been demonstrated to be safe and efficacious in protecting against severe rotavirus diarrhea among children. However, in some developing countries of Africa [8,9], Asia [10] and Central America [11] with high rotavirus prevalence, where the vaccines are most needed, these vaccines were less effective. High titers of maternal antibodies in these countries were considered to be associated with the lower immunogenicity and efficacy of these vaccines [12].…”

Epidemiological and Economic Impact of Monovalent and Pentavalent Rotavirus Vaccines in Low and Middle Income Countries

“…Many factors come into consideration, including vaccination impact on current burden of disease, vaccine prices and logistics of implementations. 12,38,39 Cost-effectiveness studies are cited as "essential" by health decision makers for introducing new vaccines; 38 however, many of the existing national immunizations advisory committees do not have the expertise on their board to fully interpret them. 38 The sustainability of new vaccines implementation in many low-income and middle-income countries is also severely limited by funding availability.…”