title: Tolerance and immunogenicity of the simultaneous administration of virosome hepatitis A and yellow fever vaccines.
abstract: BACKGROUND
  The purpose of this study was to evaluate the tolerance and immunogenicity of a hepatitis A vaccine using immunopotentiating reconstituted influenza virosomes (IRIV) as adjuvant when administered simultaneously with a yellow fever vaccine (YFV).
  
  
  METHODS
  An open prospective trial with two parallel groups was conducted with 105 volunteers to study the effect of these vaccinations on the anti-hepatitis A virus (HAV) antibody response. Half of the volunteers (53) received one dose of IRIV-HAV vaccine (Epaxal) and one dose of live attenuated YFV (Stamaril) on the same day at two different sites. Fifty-six volunteers were given a single injection of IRIV-HAV as a control group. Anti-HAV titers were measured at days 14, 28, months 3, 12, 13, and 24 using a standardized test (Enzymun test Anti-HAV). Neutralizing yellow fever antibodies were measured at days 14 and 28 for the YFV recipients. Regarding vaccine tolerance, the volunteers were asked to record all their adverse reactions on a standard report sheet for the 6 days following the immunization.
  
  
  RESULTS
  Seroconversion rates for HAV were 88% after 14 days and 100% after 4 weeks. There was no statistically significant difference between the two groups every time the titers were checked (IRIV-HAV vs HAV only: D14: 81 vs 101; D28: 275 vs 368; M3: 153 vs 169; M12: 117 vs 226; geometrical mean titers (GMT) in mIU/mL). However, lower titers were found among male volunteers, and were not attributable to YFV administration. The seroconversion rates for YFV were 90% after 14 days and 96% after 4 weeks. No serious general side-effects and only mild local reactions were reported. The administration of a booster of IRIV-HAV at 12 months resulted in a 24-fold increase in GMT.
  
  
  CONCLUSIONS
  When needed, the simultaneous administration of the IRIV-HAV and YFV is immunogenic, safe and well-tolerated, as volunteers seroconverted to both antigens, with no cross-interference.
authors.affiliation: Travel and Migration Medicine Unit, Department of Community Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: P A
authors.initials: PA
authors.lastname: Bovier
authors.forename: B
authors.initials: B
authors.lastname: Althaus
authors.forename: R
authors.initials: R
authors.lastname: Glueck
authors.forename: A
authors.initials: A
authors.lastname: Chippaux
authors.forename: L
authors.initials: L
authors.lastname: Loutan
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D003429:Cross Reactions; D005260:Female; D006507:Hepatovirus / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D011446:Prospective Studies; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D014761:Viral Hepatitis Vaccines