Comparison of anti-Vi IgG responses between two clinical studies of typhoid Vi conjugate vaccines (Vi-DT vs Vi-TT).

Abstract

Salmonella enterica serovar Typhi (S. Typhi) is a causative agent for typhoid fever and especially critical in developing countries. Although clinical studies for various typhoid conjugate vaccines (TCVs) have been performed, there are no comparative data on the immune responses of vaccines due to lack of harmonization of the serological assay. Recently, Typbar-TCV (Vi-TT) was prequalified by WHO and recommended for vaccination in endemic areas. Forty-eight serum samples were selected from a recent Vi-DT phase 1 study based on age cohort and anti-Vi IgG levels using an in-house ELISA. Anti-Vi IgG titers of 48 sera were also determined by Vacczyme ELISA, used in a Vi-TT phase 3 trial. A good correlation between the two assays was observed when the anti-Vi IgG titer was determined using Vacczyme ELISA based on the Vi-IgGR1,2011, U.S. reference reagent (Pearson correlation coefficient (r) = 0.991, P < 0.001) or Vacczyme ELISA calibrator (r = 0.991, P < 0.001). Based on the correlation, multiple linear regression model was developed to convert data of 281 sera (prior to vaccination and 28 days post first-dose) in the Vi-DT phase 1 study from in-house ELISA titers to Vacczyme ELISA values and then, compared with the Vi-TT results. Similar estimates of anti-Vi IgG GMT were observed after vaccination with the Vi-DT and Vi-TT vaccines [1626 EU/ml (95% CI: 1292–2047) vs 1293 EU/ml (95% CI: 1153–1449), respectively]. The method used here can be implemented to estimate and compare anti-Vi IgG levels between different clinical studies of TCVs. This approach enables comparison of the antibody responses among TCVs under development and may help facilitate licensing of new TCVs.