Effect of Dosage on Immunogenicity of a Vi Conjugate Vaccine Injected Twice into 2- to 5-Year-Old Vietnamese Children

Abstract

ABSTRACT In a double-blind, randomized, and placebo-controlled previous trial, the efficacy of Vi- r EPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46 months. Vi- r EPA contained 25 μg of Vi and induced a greater-than-eightfold rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25 μg of Vi- r EPA in this age group. Two doses of Vi- r EPA were injected 6 weeks apart. Blood samples were taken before and at 10 weeks (4 weeks after the second injection) and 1 year later. All postimmunization geometric mean (GM) levels were higher than the preimmune levels ( P < 0.0001). At 10 weeks, the GM IgG anti-Vi level elicited by 25 μg (102 EU/ml) was higher than those elicited by 12.5 μg (74.7 EU/ml) and 5 μg (43 EU/ml) ( P < 0.004): all of the children had ≥3.52 EU/ml (estimated minimum protective level). One year later, the levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml, P < 0.0001) but remained significantly higher than the preimmune levels ( P < 0.0001), and >96% of the children had a greater-than-eightfold rise. This study also confirmed the safety and consistent immunogenicity of the four lots of Vi- r EPA used in this and previous trials.