title: Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation.
abstract: BACKGROUND
  A refrigerator-stable rotavirus (RV) vaccine that withstands gastric acid is anticipated to permit more widespread use of RV vaccine.
  
  
  OBJECTIVE
  We investigated for the first time in infants an oral, liquid formulation of G1 and G2 human bovine reassortant rotavirus vaccine (HRRV) with a new stabilizer/buffer (S/B) containing sucrose, sodium phosphate and sodium citrate.
  
  
  METHODS
  During 1997 through 1998, 731 healthy infants approximately 2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses approximately 6 to 8 weeks apart in a partially double blinded study. Infants were randomized to: (1) HRRV with no S/B but with prefeeding; (2) HRRV plus 1 of 3 different concentrations/volumes of S/B; or (3) placebo.
  
  
  RESULTS
  No serious vaccine-related adverse experiences or intussusception cases were reported. No statistically significant differences were observed between vaccine and placebo recipients for fever (> or =38.1 degrees C) 0 to 7 days after any dose, irritability, vomiting or diarrhea incidence 0 to 42 days after any dose. Vaccine virus shedding among vaccine recipients was uncommon. Among S/B vaccine groups, proportions of infants with a > or =3-fold titer rise from baseline to Postdose 3 for G1 serum-neutralizing antibody (SNA), G2 SNA, WC3 SNA, serum anti-RV IgA, serum anti-RV IgG and stool anti-RV IgA were generally similar to those of the prefed non-S/B group.
  
  
  CONCLUSIONS
  HRRV with a new S/B was generally well-tolerated; immunogenicity was generally similar to the prefed non-S/B group. No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV.
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: H Fred
authors.initials: HF
authors.lastname: Clark
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Burke
authors.forename: David B
authors.initials: DB
authors.lastname: Volkin
authors.forename: Paul
authors.initials: P
authors.lastname: Offit
authors.forename: Richard L
authors.initials: RL
authors.lastname: Ward
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bresee
authors.forename: Penelope
authors.initials: P
authors.lastname: Dennehy
authors.forename: W Manfred
authors.initials: WM
authors.lastname: Gooch
authors.forename: Edgardo
authors.initials: E
authors.lastname: Malacaman
authors.forename: David
authors.initials: D
authors.lastname: Matson
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Walter
authors.forename: Barbara
authors.initials: B
authors.lastname: Watson
authors.forename: David L
authors.initials: DL
authors.lastname: Krah
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dallas
authors.forename: Florian
authors.initials: F
authors.lastname: Schödel
authors.forename: karen M
authors.initials: kM
authors.lastname: Kaplan
authors.forename: Penny
authors.initials: P
authors.lastname: Heaton
mesh_terms: D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D004311:Double-Blind Method; D005243:Feces / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007109:Immunity / Q000502:physiology; D007223:Infant; D008297:Male; D012016:Reference Values; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D012449:Safety; D012680:Sensitivity and Specificity; D014613:Vaccines, Attenuated / Q000008:administration & dosage
chemical_list: D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated