WASHINGTON _ The U.S. Army has begun to formulate arecombinant plague vaccine made by inserting the gene for abacterial coat protein inside an E. Coli vector that churns out largequantities of apparently protective antigen.The prototype vaccine, now being studied by researchers at the U.S.Army Medical Research Institute for Infectious Diseases(USAMRID), would be the first advance in the prevention of plaguesince the discovery of antibiotics. The only current vaccine, awhole, killed-cell vaccine now made by Greer Laboratories, inLenoir, N.C., has been used in the U.S. for 50 years.Col. Arthur Friedlander, chief of bacteriology at USAMRID andhead of the vaccine research project, said the current version is "sortof a 19th century vaccine. A similar vaccine has been used since theturn of the century."David Dennis, a plague expert at the Centers for Disease Controland Prevention's field station in Fort Collins, Colo., said the currentwhole-cell vaccine is not only old, it's unsatisfactory."It requires two doses and takes time to build up antibodies,"Dennis said. "We also recommend annual boosters, and not manypeople want to do that because the vaccine can cause fairlyunpleasant adverse reactions. It's not a pleasant vaccine to take."India's recent brush with plague focused attention on the antiquity,scarcity and adverse effects produced by the current vaccine. It alsohighlighted the need for a new vaccine, in case Yersinia Pestis, thebacteria that causes plague, stages a comeback _ along withtuberculosis, cholera and a host of resurgent organisms mankindhad believed were on the wane.No Demand For Plague Vaccine _ In U.S.The lack of a state-of-the-art vaccine stems in part from the lack ofdemand for plague vaccine in the U.S., even though a handful ofcases crop up in New Mexico and other Southwestern states eachyear. So far only the Army _ which worries both about thepotential use of Yersinia Pestis as a germ warfare agent and aboutendemic plague in battle-torn areas _ purchases large quantities ofplague vaccine, about 20,000 doses a year."The Armed Forces are the only people who have a use for thevaccine because the disease is so rare that there is no reason toimmunize the general population," said Patrick Murphy, a professorof medicine at the Johns Hopkins Medical School, in Baltimore.But even the Army's allotment is small compared with the millionsof doses produced each year of measles, diphtheria and other morecommonly used vaccines.The prototype recombinant vaccine was developed by researchers atthe U.S. Public Health Service Rocky Mountain Laboratories inHamilton, Mont., who a few years ago began to study the moleculargenetics of plague and its host, the flea.Tom Schwan, who heads the project, said the work began threeyears ago when post-doctoral researcher Warren Simpsonsucceeded in cloning the gene for the capsular antigen for YersiniaPestis, a coating that the bacterium dons in the human host as aprotection against the stalwart white blood cells known asphagocytes that are charged with destroying invading organisms.Simpson then loaded the gene into a plasmid and inserted theplasmid into E. Coli, which began producing capsule proteins.Initial tests demonstrated the promise of the new approach, Schwansaid. "We used it in mice and it was protective."Enter Col. Friedlander, of USAMRID, who heard Simpson deliveran address about the vaccine at a medical meeting shortly after thefirst experiments were carried out.Friedlander said he requested the material so that his lab could carryout its own experiments. So far, the Army researchers have insertedthe coating gene into a new, more stable strain of E. Coli, which ischurning out a higher quantity of the antigen. Preliminary studieshave demonstrated that the vaccine does indeed protect againstplague infection.Most likely, Friedlander said, the Army will couple the vaccine withothers in a multiplex format and license it to a private biotechcompany to produce. But the vaccine is still in the early stages ofdevelopment, and licensing is probably years away, he said. n
-- Steve Sternberg Special To BioWorld Today
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