title: The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines.
abstract: Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Vu Dinh
authors.initials: VD
authors.lastname: Thiem
authors.forename: Feng-Ying C
authors.initials: FY
authors.lastname: Lin
authors.forename: Do Gia
authors.initials: DG
authors.lastname: Canh
authors.forename: Nguyen Hong
authors.initials: NH
authors.lastname: Son
authors.forename: Dang Duc
authors.initials: DD
authors.lastname: Anh
authors.forename: Nguyen Duc
authors.initials: ND
authors.lastname: Mao
authors.forename: Chiayung
authors.initials: C
authors.lastname: Chu
authors.forename: Steven W
authors.initials: SW
authors.lastname: Hunt
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
authors.forename: Shousun C
authors.initials: SC
authors.lastname: Szu
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014744:Vietnam; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C057664:Vi polysaccharide vaccine, typhoid