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Infection and Immunity, November 1999, p. 5806-5810, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Safety and Immunogenicity of Vi Conjugate Vaccines for Typhoid
Fever in Adults, Teenagers, and 2- to 4-Year-Old Children in
Vietnam
Zuzana
Kossaczka,1
Feng-Ying C.
Lin,1
Vô Anh
Ho,2
Nguyen Thi Thanh
Thuy,3
Phan
Van
Bay,2
Tran Cong
Thanh,3
Ha Ba
Khiem,3
Dang Duc
Trach,4
Arthur
Karpas,1
Steven
Hunt,1
Dolores A.
Bryla,1
Rachel
Schneerson,1
John B.
Robbins,1 and
Shousun
C.
Szu1,*
National Institutes of Health, Bethesda, Maryland
20892,1 Huu Nghi Hospital, Cao
Lânh District, Dong Thap Province,2
Pasteur Institut, Ho Chi Minh City,3 and
National Institute of Hygiene and Epidemiology,
Hanoi,4 People's Republic of Vietnam
Received 7 June 1999/Returned for modification 13 July
1999/Accepted 13 August 1999
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-rEPA1) or adipic acid dihydrazide (ADH;
Vi-rEPA2) as linkers. None of the recipients
experienced a temperature of >38.5°C or significant local reactions.
One injection of Vi-rEPA2 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-rEPA2, Vi-rEPA1, and
Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA1 and Vi with respect to
Vi-rEPA2). At 26 weeks, the anti-Vi IgG levels
for recipients of Vi-rEPA2,
Vi-rEPA1, and Vi were 30.0, 10.8, and 13.4 EU,
respectively (P < 0.001 for
Vi-rEPA1 and Vi with respect to
Vi-rEPA2); all were higher than the
preinjection levels (P = 0.0001).
Vi-rEPA2 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-rEPA2 elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA1
(P = 0.0001). Reinjection increased Vi antibody levels
from 69.9 to 95.4 EU for Vi-rEPA2 and from 28.9 to 83.0 EU for Vi-rEPA1. At 26 weeks, anti-Vi
IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA2 and 12.8 versus 0.33 for
Vi-rEPA1; 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-rEPA2 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-rEPA2
conjugate warrant further investigation.
*
Corresponding author. Mailing address: National
Institutes of Health, Bethesda, MD 20892. Phone: (301) 496-4524. Fax:
(301) 402-9108. E-mail: scszu{at}helix.nih.gov.
Infection and Immunity, November 1999, p. 5806-5810, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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