Salmonella typhi vaccine
Organizations involved (only one prominent early developer listed):
U.S. Army – R&D
Cross ref.: See the entries below for typhoid vaccines.
Description: Typhoid vaccines incorporate Salmonella typhi (S. typhosa) antigens to induce prophylactic immunity against typhoid fever (due to S. typhi infection). Typhoid vaccines are administered to persons traveling to or residing in areas where typhoid fever is endemic, including many lesser-developed and tropical countries.
Three typhoid vaccines have been approved in the U.S. – an older inactivated S. typhi whole cell injected vaccine (no longer approved); a live attenuated S. typhi oral vaccine; and a purified S. typhi Vi polysaccharide injected vaccine. Each has some limitations. The inactivated whole cell vaccine has a higher reactogenicity than the other two, which are better tolerated. The live oral vaccine requires four doses in the U.S. and Canada (three doses in most other countries), which hinders compliance (completion of the regimen). The polysaccharide vaccine has only about 50% efficacy at three years and is not very immunogenic in infants.
An Acetone-Inactivated/Killed, Dried (AKD) S. typhi vaccine manufactured by Wyeth, similar to the company’s current phenol- and heat-inactivated vaccine, has been available (apparently under an IND) for use by the U.S. Department of Defense (DOD) for vaccinating military personnel.
Nomenclature: Typhoid Vaccine [FDA]; typhoid fever vaccine [SY]; Anti-Typhoid Vaccine [FDA former]; Salmonella typhi vaccine [SY]
History: During the Spanish-American War of 1898, the U.S. experienced only 243 battle fatalities, but 20,738 cases of typhoid fever. The first typhoid vaccine studies in the U.S. were conducted by Dr. F. Russell, U.S. Army Medical School, and collaborators. Typhoid-fever vaccination became compulsory in 1911 for the U.S. military, and remains compulsory. During World War I, a mere 1,529 cases of typhoid fever were reported, including 227 deaths, among 4.13 million Americans in the military. Companies previously licensed to manufacture Typhoid Vaccine (according to the CBER/FDA database): Bayer Corp. (March 1916-Oct. 1970); Eli Lilly & Co. (Feb. 1954-Nov. 1978); Massachusetts Public Health Biologic Labs. (March 1917-Oct. 1988); Merck & Co., Inc. (April 1963-Jan. 1986); Michigan Biologic Products Inst. (July 1926-June 1985); Parke-Davis Div., Warner-Lambert Co. (March 1916-Feb. 1959); and the Texas Dept. of Health (July 1950-Feb. 1979). Another FDA source reports that Anti-Typhoid Vaccines, presumably whole inactivated vaccines, from Burroughs Wellcome & Co. and the Swiss Serum and Vaccine Institute Berne were approved in 1908.
Beginning in the 1950s, human typhoid vaccine challenge studies, involving purposeful infection with S. typhi, were conducted by the University of Maryland School of Medicine on hundreds of adult male inmates at a Maryland correctional facility (Jessup, MD). These studies were terminated in 1974.
Status: Typhoid vaccines are described in the Code of Federal Regulations, Tittle 21, Section 610.2 (21 CFR 610.21). The vaccines must contain at least 8 units/mL.
The Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC), recom-mends typhoid vaccination prior to travel to areas with endemic typhoid fever, with preference for the oral Ty21A and the Vi capsular polysaccharide vaccines due to their less reacto-genicity than the whole cell vaccine.
Trials: Original approvals of the three typhoid vaccines were based on results of well controlled field efficacy studies, with protective efficacy demonstrated by testing in highly endemic areas. Comparative efficacy studies of the typhoid vaccines have not been performed.
Disease: In the U.S,, about 3-400 cases of typhoid fever occur each year, with about 70% of these acquired while traveling internationally. Other unreported cases may occur among Americans in foreign countries. Nearly all cases occur among unvaccinated persons.
Typhoid fever reemerged as a health threat in the 1990s. Salmonella typhi generally does not carry plasmids, which can confer antibiotic resistance. However, it does accept plasmids of incompatibility Group H1. Strains now found in the Indian subcontinent, Middle East, Northeast Africa, and Southeast Asia are carrying INK H1 plasmids that confer resistance to chlor-amphenicol, trimethaprim sulfur methoxizol, and amoxy-cillin (antibiotics that were the among the primary drugs of choice starting in the 1980s). Development of antibiotic resistant strains of S. typhi makes vaccination more important.
R&D: Various organizations are developing new typhoid vaccines, e.g., Microscience Ltd. (Berkshire, U.K.) has been conducting trials with an oral typhoid vaccine. Emergent BioSolutions Inc. is developing a single dose oral typhoid vaccine, with a vaccine entering trials in 2006. AVANT Immunotherapeutics, Inc., now Celldex Therapeutics, Inc., is developing Ty800, a single-dose live oral vaccine using attenuated (gene-deleted) S. typhi. USV Ltd. is developing a new conjugate capsular polysaccharide typhoid vaccine initially developed at the All India Institute of Medical Sciences (AIIMS). Sanofi-Pasteur and NIH were developing a rPAE-Vi conjugate vaccine in Phase II/III testing in 2006. Live attenuated oral CVD908-htrA and CVD 909 being developed by the University of Maryland and Acambis/Berna were in Phase II trials in 2006. Biovel Life Sciences is developing a polysaccharide vaccine for typhoid.
Index Terms:
Companies involvement:
Full monograph
560 Typhoid Vaccine Products
Nomenclature:
Typhoid Vaccine Products [FDA]
typhoid vaccine [SY]
Anti-Typhoid Vaccine [FDA former]
Salmonella typhi vaccine [SY]
biopharmaceutical products
vaccines, bacterial
vaccines, live
bacterial culture <!-- bacterialculture -->
saline-adenine-glucose
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