title: Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.
abstract: BACKGROUND
  RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth.
  
  
  METHODS
  A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis.
  
  
  RESULTS
  The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant.
  
  
  CONCLUSIONS
  A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials.
authors.affiliation: RV3 Rotavirus Vaccine Program, Murdoch Childrens Research Institute, Parkville, Victoria, Australia. margie.danchin@rch.org.au
authors.forename: M
authors.initials: M
authors.lastname: Danchin
authors.forename: C D
authors.initials: CD
authors.lastname: Kirkwood
authors.forename: K J
authors.initials: KJ
authors.lastname: Lee
authors.forename: R F
authors.initials: RF
authors.lastname: Bishop
authors.forename: E
authors.initials: E
authors.lastname: Watts
authors.forename: F A
authors.initials: FA
authors.lastname: Justice
authors.forename: V
authors.initials: V
authors.lastname: Clifford
authors.forename: D
authors.initials: D
authors.lastname: Cowley
authors.forename: J P
authors.initials: JP
authors.lastname: Buttery
authors.forename: J E
authors.initials: JE
authors.lastname: Bines
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D004311:Double-Blind Method; D005243:Feces / Q000821:virology; D005260:Female; D005838:Genotype; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology* / Q000502:physiology; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; C109545:RV3 rotavirus vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated; C049937:anti-IgA