Combined Vaccination against Hepatitis A, Hepatitis B, and Typhoid Fever: Safety, Reactogenicity, and Immunogenicity

Background The etiological agents of hepatitis A, hepatitis B, and typhoid fever share similar patterns of global distribution, and cause significant disease burden in travelers to endemic countries. Combined vaccination against all three diseases, based on currently available vaccines, would promote compliance and convenience for travelers. This clinical study evaluated the feasibility of extemporaneously syringe-mixed hepatitis A and B vaccine (Twinrix) and a Vi polysaccharide vaccine (Typherix) in healthy adults, and compared this to concomitant administration of the vaccines in separate arms. Methods The mixed dose of vaccine contained at least 720 enzyme-linked immunosorbent assay (ELISA) units of the inactivated hepatitis A antigen, 20 μg of the recombinant hepatitis B antigen and 25 μg of the Vi polysaccharide typhoid antigen in 1.5 mL. The study was conducted in 200 healthy 18- to 45-year-old volunteers. Results Equivalence between the vaccines mixed before administration and the concomitantly administered vaccines was shown in terms of seroconversion and seroprotection. With the exception of local injection site soreness, which was higher in the mixed administration group, the reactogencity was similar for both groups. In both vaccination groups more than 95% of the subjects were anti-hepatitis A virus and anti-Vi seropositive 1 month after the first vaccination. With regard to hepatitis B, a strong response was achieved in both groups, with more than two-thirds of the subjects protected 2 months after the start of the immunization course. Conclusion These results support the feasibility of extemporaneously syringe-mixed combined hepatitis A and B vaccine with a Vi polysaccharide typhoid vaccine, administered in healthy adults.