title: Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.
abstract: Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.
authors.affiliation: a I nstituto de Genética Humana; Facultad de Medicina ; Pontificia Universidad ; Javeriana , Bogotá
authors.forename: Juana
authors.initials: J
authors.lastname: Angel
authors.forename: A Duncan
authors.initials: AD
authors.lastname: Steele
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Franco
mesh_terms: D057134:Antibodies, Neutralizing / Q000032:analysis; D000914:Antibodies, Viral / Q000032:analysis; D023381:Endpoint Determination; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D012401:Rotavirus / Q000276:immunology; D022243:Rotavirus Vaccines / Q000276:immunology*; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D022243:Rotavirus Vaccines
keywords: ASC, antibody secreting cells; CO, cutoff; CoP, correlate of protection; EMA, European Medicines Agency; GAVI, Global Alliance for Vaccines and Immunisation; GE, gastroenteritis; GMT, geometric mean titers; HAI, haemagglutination inhibition; IgA; MenC, Meningococcal serogroup C; RRV-TV, Rhesus RV-Tetravalent vaccine; RV, rotavirus; RV-NA, RV specific neutralizing antibodies; RV-SIg, rotavirus secretory Ig; RV-T cells, rotavirus specific T cells; RV1, Rotarix®; RV5, RotaTeq®; RV5-precursor, RV5 precursor reassortants; SBA, serum bactericidal assay; SGE, severe gastroenteritis; VE, vaccine efficacy; VEI, VE estimated with an immunological endpoint; WHO, World Health Organization; correlates of protection; mBc, memory B cells; mucosal; rSAB, serum bactericidal assay using rabbit serum; rotavirus; vaccines