Development of Vi conjugate - a new generation of typhoid vaccine.
Author(s): Szu SC.
Affiliation(s): Author information:
Eunice Kennedy Shriver National Institute of Child Health & Human Development,
National Institutes of Health, 9402 Wildoak Drive, Bethesda, Maryland, MD 20814,
USA.
Publication date & source: 2013, Expert Rev Vaccines. , 12(11):1273-86
Typhoid fever remains to be a serious disease burden worldwide with an estimated
annual incidence about 20 million. The licensed vaccines showed moderate
protections and have multiple deficiencies. Most important of all, none of the
licensed typhoid vaccines demonstrated protection for children under 5 years old.
These limitations impeded successful implementation of typhoid vaccination
programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant
exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer
lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas.
In school-age children and adults, the immunity persisted more than 8 years. In a
double-blind, placebo-controlled and randomized efficacy trial in 2- to
5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid
fever and the protection lasted at least 4 years. When given concomitantly with
infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference
with the routine vaccines. Vi conjugate vaccine was also attempted and
successfully demonstrated by several other laboratories and manufactures. Using
either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid,
recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was
significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid
conjugates were licensed in India for all ages, starts as young as 3 month old.
This new generation of typhoid vaccine opens up a new era for typhoid prevention
and elimination.
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