title: Safety, Tolerability and Immunogenicity of Pentavalent Rotavirus Vaccine Manufactured by a Modified Process.
abstract: Rotavirus is the leading cause of severe diarrhea in infants and young children. The current formulation of pentavalent rotavirus vaccine (RV5) must be stored refrigerated at 2-8°C. A modified formulation of RV5 (RV5mp) has been developed with stability at 37°C for 7 days and an expiry extended to 36 months when stored at 2-8°C.
  
  
  
  This study (ClinicalTrials.gov identifier: NCT01600092; EudraCT number: 2012-001611-23) evaluated the safety, tolerability and immunogenicity of RV5mp versus the currently marketed RV5 in infants. To maintain blinding, both vaccine formulations were stored refrigerated at 2-8°C for the duration of the study. Immunogenicity endpoints were (1) serum neutralizing antibody titers to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and (2) proportion of subjects with a ≥3-fold rise from baseline for serum neutralizing antibody to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and serum antirotavirus immunoglobulin A.
  
  
  
  The RV5mp group (n = 505) and RV5 group (n = 509) had comparable safety profiles. There were no deaths and no vaccine-related serious adverse events in this study. With respect to immunogenicity, RV5mp was noninferior compared with RV5. Serum neutralizing antibody responses by country and breast-feeding status were generally consistent with the overall results.
  
  
  
  RV5mp enhances storage requirements while maintaining the immunogenicity and safety profile of the currently licensed RV5. A vaccine that is stable at room temperature may be more convenient for vaccinators, particularly in places where the cold chain is unreliable, and ultimately will permit more widespread use.
authors.affiliation: From the *Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain; †Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Instituto de Investigación Sanitaria de Santiago and Universidade de Santiago de Compostela (USC), Galicia, Spain; §Soroka University Medical Center, Pediatric Infectious Disease Unit, Beer Sheva, Israel; ¶Department of Pediatrics, Creighton University, Omaha, Nebraska; and ‖Merck & Co., Inc., Merck Research Laboratories, Kenilworth, New Jersey.
authors.forename: Federico
authors.initials: F
authors.lastname: Martinón-Torres
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.forename: Meera
authors.initials: M
authors.lastname: Varman
authors.forename: John A
authors.initials: JA
authors.lastname: Killar
authors.forename: Darcy
authors.initials: D
authors.lastname: Hille
authors.forename: Erica L
authors.initials: EL
authors.lastname: Strable
authors.forename: Jon E
authors.initials: JE
authors.lastname: Stek
authors.forename: Susan S
authors.initials: SS
authors.lastname: Kaplan
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology; D022243:Rotavirus Vaccines / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated