Tolerance and immunogenicity of the simultaneous administration of virosome hepatitis A and yellow fever vaccines.

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.