title: Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam.
abstract: The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using either N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA(1)) or adipic acid dihydrazide (ADH; Vi-rEPA(2)) as linkers. None of the recipients experienced a temperature of >38.5 degrees C or significant local reactions. One injection of Vi-rEPA(2) into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA(2), Vi-rEPA(1), and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA(2), Vi-rEPA(1), and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)); all were higher than the preinjection levels (P = 0. 0001). Vi-rEPA(2) also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA(2) elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA(1) (P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA(2) and from 28.9 to 83.0 EU for Vi-rEPA(1). At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA(2) and 12.8 versus 0.33 for Vi-rEPA(1); P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA(2) in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA(2) conjugate warrant further investigation.
authors.affiliation: National Institutes of Health, Bethesda, Maryland 20892, People's Republic of Vietnam.
authors.forename: Z
authors.initials: Z
authors.lastname: Kossaczka
authors.forename: F Y
authors.initials: FY
authors.lastname: Lin
authors.forename: V A
authors.initials: VA
authors.lastname: Ho
authors.forename: N T
authors.initials: NT
authors.lastname: Thuy
authors.forename: P
authors.initials: P
authors.lastname: Van Bay
authors.forename: T C
authors.initials: TC
authors.lastname: Thanh
authors.forename: H B
authors.initials: HB
authors.lastname: Khiem
authors.forename: D D
authors.initials: DD
authors.lastname: Trach
authors.forename: A
authors.initials: A
authors.lastname: Karpas
authors.forename: S
authors.initials: S
authors.lastname: Hunt
authors.forename: D A
authors.initials: DA
authors.lastname: Bryla
authors.forename: R
authors.initials: R
authors.lastname: Schneerson
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
authors.forename: S C
authors.initials: SC
authors.lastname: Szu
mesh_terms: D036002:ADP Ribose Transferases; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000009:adverse effects / Q000276:immunology*; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000276:immunology*; D002675:Child, Preschool; D005098:Exotoxins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D011135:Polysaccharides, Bacterial / Q000009:adverse effects / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D005098:Exotoxins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A