This is a highly effective vaccine suitable for children and should find utility in endemic regions and as a traveler's vaccine.

This invention is a method of immunization against typhoid fever using a conjugate vaccine comprising the capsular polysaccharide of Salmonella typhi, Vi, conjugated through an adipic dihydrazide linker to nontoxic recombinant exoprotein A (rEPA) from Pseudomonas aeruginosa.  The three licensed vaccines against typhoid fever, attenuated S. typhi Ty21a, killed whole cell vaccines and Vi polysaccharide, have limited efficacy, in particular for children under 5 years of age, which make an improved vaccine desirable. 

 

It is generally recognized that an effective vaccine against Salmonella typhi is one that increases serum anti-Vi IgG eight-fold six weeks after immunization.  The conjugate vaccine of the invention increases anti-Vi IgG, 48-fold, 252-fold and 400-fold in adults, in 5-14 years-old and 2-4 years-old children, respectively.  Thus this is a highly effective vaccine suitable for children and should find utility in endemic regions and as a traveler's vaccine.  The route of administration can also be combined with routine immunization.  In 2-5 years old, the protection against typhoid fever is 90% for 4 years.  In school age children and in adults the protection could mount to completer protection according to the immunogenicity data.

 

Application: 

Immunization against Salmonella typhi for long term prevention of typhoid fever in all ages.

 

Developmental Status: 

Conjugates have been synthesized and clinical studies have been performed.  The synthesis of the conjugates is described by Kossaczka et al. in Infect Immun. 1997 Jun;65(6):2088-2093 [PubMed abs].  Phase III clinical studies are described by Mai et al. in N Engl J Med. 2003 Oct 2; 349(14):1390-1391 [PubMed].  Dosage studies are described by Canh et al. in Infect Immun. 2004 Nov;72(11):6586-6588 [PubMed abs]. 

 

A safety and immunogenicity study in infants are underway.  The aim is to administer the conjugate vaccine with routine infant immunization.  Preliminary results show the vaccine is safe in 2 months old infants.

·   U.S. Patent 6,797,275 issued 28 Sep 2004 (HHS Reference No. E-020-1999/0-US-02)

·   U.S. Patent Application No. 10/866,343 filed 10 Jun 2004 (HHS Reference No. E-020-1999/0-US-03)

Inventors: 

Zuzana Kossaczka, Shousun C. Szu, and John B. Robbins (NICHD)

Licensees Sought:

Available for non-exclusive licensing.

 

Collaborative Research Opportunity: 

The National Institute of Child Health and Human Development, Laboratory of Developmental and Molecular Immunity, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize A Method of Immunizing Humans Against Salmonella Typhi Using a Vi-rEPA Conjugate Vaccine.  Please contact John Hewes, Ph.D., at 301-496-0477 or hewesj@mail.nih.gov for more information.