COMMERCIALIZE CAPSULAR POLYSACCHARIDEVACCINES
By David N. LeffScience Editor
Fruit pectin is the once-familiar substance our grandmothers used tomake jelly jell. In fact, pectin's name comes from the Greek pektos,meaning "coagulated."
Now a laboratory at the National Institute of Child Health andHuman Development (NICHD) is using fruit pectin as a basicingredient in making vaccines against typhoid fever.
This improbable recipe begins, essentially, by mixing pectinextracted from the inner rind of citrus fruit with acetyl, the mainchemical constituent of acetic acid _ vinegar. It then combines theresulting acetylated hydroxyl groups of the pectin with a non-toxictetanus toxoid protein.
Pectin is a high-molecular-weight substance consisting mainly ofgalacturonic acids joined in long chains. Recent research at theNICHD's Laboratory of Developmental and Molecular Immunityrevealed that the chemical structure of acetylated pectin mimics thatof a portion of Salmonella typhi, the pathogen of typhoid fever.
More to the point, the acetylated pectin's linear polymer cross-reactsimmunologically with the bacterium'svirulence-antigen capsular polysaccharide. As for the tetanus protein,explains Shousson Szu of the NICHD laboratory, "the capsularpolysaccharide hitchhikes on the tetanus toxin protein, so when youimmunize with it, the T cells of the immune system sees the twocomponents as one."
Szu is first author of a paper in the December 1994 issue of Infectionand Immunity, describing this synthesis of a typhoid fever vaccinewhich she and co-author Slavomir Bystrisky, a visiting scientist fromthe Slovak Academy of Sciences, Bratislava, developed jointly
"Polysaccharides are not usually very good immunogens," Bystriskytold BioWorld Today. "Capsular polysaccharide is a big molecule. Itlies on the bacterium's outer surface, exposed to the immunesystem's antibodies."
"We are ready to do Phase I trials of the vaccine," Szu toldBioWorld Today, probably here at the National Institutes of Health."She explained that "Volunteers will be injected with 25 microgramsof capsular polysaccharide, and bled four weeks later to check theirlevel of antibodies against the bacterial antigen."
Szu and Bystrisky also are co-inventors of an issued U.S. patent, No.5,204,098, dated April 20, 1993, which covers their generaltechnology of "conjugates of pathogenic organism capsularpolysaccharides and proteins useful as vaccines." Its broadest claimreads: "A composition for enhancing the antibody response of a hostcomprising a capsular polysaccharide having carboxyl groupsconjugated . . . to a protein in a physiologically acceptable carrier."
On Oct. 17, 1994, the NIH Office of Technology Transfer (OTT)filed for a patent on their typhoid fever vaccine (Serial No.08/323,918). And this week, OTT forwarded an announcement forpublication in the Federal Register inviting biotechnology andpharmaceutical companies to seek licenses for commercializing theinvention.
One such conjugate, having capsular polysaccharides fromStaphylococcus, has already been licensed exclusively to UnivaxBiologics Inc., of Rockville, Md., OTT contract specialist RobertBenson told BioWorld Today.
Still available are the two inventions described above, and thefollowing four patent-pending discoveries covering these conjugates:
Detoxified flipopolysaccharide rom Vibrio cholerae, in Phase I trialwith 38 volunteers, elicited "higher levels of antibody than whole-cell vaccine."
Pertussis toxin used as a carrier protein with Streptococcuspneumoniae. Conjugates raised antibodies against bacterial antigensand toxoid proteins both.
Filing Date: 8/21/92.
Serial Number: 07,932,960.
Conjugate of E. coli capsular polysaccharide with carrier proteinsraised antibodies to Neisseria meningitidis, "a potent vaccine againstGroup B meningitis."
Filing Date: 3/12/91.
Serial Number: 08/153.263
Cryptococcus neoformans is an encapsulated fungus, with a highincidence of infection in AIDS patients. Conjugates of its capsularpolysaccharide with carrier proteins makes a vaccine now in clinicaltrials.
Editor's Note: For information concerning licensure of theseinventions, consult Robert Benson, contract specialist, NIH Office ofTechnology Transfer, (301) 496-7735, Ext. 267.
(c) 1997 American Health Consultants. All rights reserved.