Establishment of the first International Standard for human anti-typhoid capsular Vi polysaccharide IgG

Abstract

Vi capsular polysaccharide (Vi) conjugate vaccines, which can prevent typhoid in infants and young children, are being developed. Comparative immunogenicity studies are facilitated by an International Standard (IS) for human anti-Vi IgG. 16/138, a pool of sera from volunteers which received either Vi conjugate vaccine or plain Vi vaccine, was assessed as an IS alongside U.S. reference reagent Vi-IgG_{R1, 2011}. Samples were tested in a commercial ELISA (n = 7), a standardised ELISA based on biotinylated Vi (n = 7) and in-house ELISAs (n = 7). Valid estimates were obtained for the potency of all samples in the commercial ELISA, and the commutability of 16/138 and Vi-IgG_{R1, 2011} was evident for the commercial ELISA and in-house ELISAs based on a coating of Vi and protein. The WHO Expert Committee on Biological Standardization established 16/138 as the first IS for anti-Vi IgG with 100 IU per ampoule and assigned 163 IU per vial of Vi-IgG_{R1, 2011}.

Keywords: ELISA; IgG; International standard; Polysaccharide; Typhoid; Vi.

Fig. 1

Titration of anti-Vi IgG in liquid (△) and freeze dried (■) formulations of 16/138 by the NIBSC ELISA.

Fig. 2

Boxplot of potencies of samples Vi-IgG_{R1, 2011} and A to E relative to 16/138 in NIBSC and VaccZyme ELISAs.

Fig. 3

Scatterplots of log potencies relative to 16/138 in VaccZyme (Vacc) and in-house ELISAs (IH) for individual lab pairs; solid line indicates agreement, dashed line indicates fitted Deming regression.

Fig. 4

Scatterplots of log potencies relative to 16/138 in NIBSC and in-house ELISAs (IH) for individual lab pairs; solid line indicates agreement, dashed line indicates fitted Deming regression.

Fig. 5

Boxplot of log potencies of study samples calculated relative to 16/138 (assigned 100 IU per ampoule) or Vi-IgG_{R1, 2011} (assigned 163 IU per vial) in VaccZyme ELISAs (V) and in-house ELISAs by Laboratories 1, 4 and 5 (IH).