title: 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.
abstract: 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.
  
  
  BACKGROUND
  CTRI/2011/08/001957, CTRI/2014/01/004341.
authors: Bharat Biotech International Limited, Hyderabad, Telangana, India.
authors: Vadrevu Krishna
authors: VK
authors: Mohan
authors: Bharat Biotech International Limited, Hyderabad, Telangana, India.
authors: Vineeth
authors: V
authors: Varanasi
authors: Bharat Biotech International Limited, Hyderabad, Telangana, India.
authors: Anit
authors: A
authors: Singh
authors: Centre for Vaccine Development, University of Maryland School of Medicine, Baltimore.
authors: Marcela F
authors: MF
authors: Pasetti
authors: Centre for Vaccine Development, University of Maryland School of Medicine, Baltimore.
authors: Myron M
authors: MM
authors: Levine
authors: Bharat Biotech International Limited, Hyderabad, Telangana, India.
authors: Ramasamy
authors: R
authors: Venkatesan
authors: Bharat Biotech International Limited, Hyderabad, Telangana, India.
authors: Krishna M
authors: KM
authors: Ella
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D019353:Endemic Diseases / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000009:adverse effects* / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C057664:Vi polysaccharide vaccine, typhoid
keywords: avidity; booster; conjugate vaccine; persistence; typhoid