Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study

Clin Infect Dis. 2015 Aug 1;61(3):393-402. doi: 10.1093/cid/civ295. Epub 2015 Apr 13.


Background: Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age.

Methods: Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion [SCN]) 42 days after immunization.

Results: Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95% CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI], 60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed.

Conclusions: Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups.

Clinical trials registration: CTRI/2011/08/001957, CTRI/2014/01/004341.

Keywords: avidity; booster; conjugate vaccine; persistence; typhoid.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Endemic Diseases / prevention & control*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Infant
  • Male
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • Typhoid Fever / prevention & control*
  • Typhoid-Paratyphoid Vaccines / adverse effects*
  • Typhoid-Paratyphoid Vaccines / immunology*
  • Vaccines, Conjugate / adverse effects*
  • Vaccines, Conjugate / immunology*


  • Antibodies, Bacterial
  • Immunoglobulin G
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Conjugate
  • Vi polysaccharide vaccine, typhoid

Associated data

  • CTRI/2011/08/001957
  • CTRI/2014/01/004341