Tolerance and Immunogenicity of the Simultaneous Administration of Virosome Hepatitis A and Yellow Fever Vaccines

Authors

  • Patrick A. Bovier,

    Corresponding author
    1. Patrick A. Bovier, MD, MPH: Travel and Migration Medicine Unit, Department of Community Medicine, Geneva University Hospital, Geneva, Switzerland
      Reprint requests: Patrick A. Bovier, MD, MPH: Travel and Migration Medicine Unit, Department of Community Medicine, Geneva University Hospital, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.
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  • Beat Althaus,

    1. Beat Althaus, MD and Reinhard Glueck, PhD: Swiss Serum and Vaccine Institute Berne, Switzerland
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  • Reinhard Glueck,

    1. Beat Althaus, MD and Reinhard Glueck, PhD: Swiss Serum and Vaccine Institute Berne, Switzerland
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  • André Chippaux,

    1. André Chippaux, MD: Institut Pasteur, Unité des Arbovirus et Virus des Fièvres Hémorragiques, Paris, France
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  • Louis Loutan

    1. Louis Loutan, MD, MPH: Travel and Migration Medicine Unit, Department of Community Medicine, Geneva University Hospital, Geneva, Switzerland.
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Reprint requests: Patrick A. Bovier, MD, MPH: Travel and Migration Medicine Unit, Department of Community Medicine, Geneva University Hospital, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.

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 (EpaxalTM) and one dose of live attenuatedYFV (StamarilTM) on the same day at two different sites. Fiftysix 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 mlU/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.

Conclusion: 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.

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