MEDIMMUNE NOMINATES DARK-HORSE VACCINE CANDIDATE AGAINST LYME DISEASE

Editor's note: Science Scan is a round-up of recently publishedbiotechnology-related research.

A new, and possibly improved, candidate vaccine against Lymedisease made its bow last Friday at the Seventh InternationalCongress on Lyme Borreliosis, in San Francisco.

Molecular microbiologist Mark Hanson of MedImmune Inc., inGaithersburg, Md. reported to the week-long meeting's closingsession that "Antibodies against the Borrelia burgdorferi decorinbinding protein [DBP] protect mice from challenge."

Scientists at Texas A&M University, in Houston, discovered DBP in1993, and determined the protein's gene sequence in 1995.MedImmune shared in the research effort, and received an exclusivelicense to the previously unknown protein, which binds to a humanprotein called decorin.

"Decorin is so-called," the firm's manager of strategic planning andinvestor relations, Mark Kaufmann, told BioWorld Today, "becauseit `decorates' the collagen in human skin, cartilage and tendons." Henoted that "Borrelia bacteria infect the skin, and get into cartilagetissue, where they start an inflammatory reaction that can lead toarthritis."

Kaufmann added that "the circular bull's-eye rash, a hallmark ofLyme disease, is really an inflammatory reaction against thebacterium in the skin."

How it gets there "is still unknown," he said, "but one theoryattributes the mechanism to decorin binding protein."

This is the bacterial antigen that MedImmune is studying in mice as apossible vaccine in humans.

"Decorin binding protein," Hanson said, "is the first Lyme diseasevaccine candidate discovered from the bacterium that has thepotential to be relevant for worldwide use, and induces antibodies inour animal models that are protective days after initial infection."

That is reportedly more than can be said for the current candidatevaccine now in the clinic at three companies, including MedImmuneitself.

This is Outer Surface Protein A (OspA), tested in two recentlycompleted Phase III clinical trials sponsored respectively bySmithKline Beecham plc, of Philadelphia, and ConnaughtLaboratories Inc., of Swiftwater, Pa.

MedImmune's human trial of OspA is in Phase I. "The differencebetween ours and the other two," Kaufmann observed, "is thatMedImmune's is based on a live vector vaccine, BCG, and theirs ona subunit protein."

Scientists in several laboratories recently have found that the OspAantigen may be expressed on the surface of B. burgdorferi only whenthe bacterium is inside the tick. As the tick feeds on its human host,into whom it injects the bacterium, the antigen is lost. Hence, anOspA-based vaccine must be administered almost immediately afterthe bite.

Hanson reported that, "Unlike antibodies to OspA, DBP antibodiescan be given to mice four days after infection, and still clear thebacterium from animals. This," he added, "may allow a significantlygreater window of opportunity for a protective immune response."

"If Osp is successful on its own," Kaufmann said, "then DBP could,theoretically, augment its efficacy. If Osp doesn't work, one coulduse DBP alone."

Should ongoing preclinical immunization studies continue promising,he concluded, "we would scale up production for potential INDsubmission to the FDA, aimed at Phase I human trials in 1997."

Slovenian Clinicians Report FirstClear-Cut HIV Transmission By Bite

Can human teeth transmit the AIDS virus, and infect the personbitten?

All 13 cases reported to date in the medical literature have remainedseronegative, according to a letter in the latest The Lancet, dated June22, 1996. Its author, microbiologist Ludvik Vidmar, is on the medicalfaculty at the University of Lubljana, Slovenian Republic.

Vidmar reports "clearly documented HIV seroconversion thatoccurred after a bite." This is the scenario his communicationdescribed:

* On May 12, 1995, a 47-year-old homosexual man with terminalAIDS, and lymphoma of the brain, had an epileptic seizure.Frightened, he went to a neighbor, where he sustained another fit.

* The 53-year-old neighbor, unaware of the patient's diagnosis,inserted his fingers in the man's mouth to prevent him fromswallowing his tongue and choking _ a common feature of gran malseizures.

* Whereupon, the neighbor suffered a small bite that cracked onefingernail, and left bloodless tooth marks on his skin. He noticedblood in the saliva on the biter's lips.

* The neighbor washed his hands half an hour after the incident, butwithout using soap, detergents or disinfectants. His serum, drawn thatday, revealed no HIV antigens, antibodies or DNA. As a precaution,he was started on AZT prophylaxis.

* Serological testing 54 days later revealed he had completelyseroconverted to HIV-positive state. Exhaustive inquiries as to hispersonal history and lifestyle revealed no hint of pre-existing HIVrisk factors.

* The AIDS patient died of his disease 13 days after the bitingepisode. n

"In his terminal stage," Vidmar concluded, "he may have had a highviral load, which caused a relatively short time to elapse beforeseroconversion in the bitten man." n

Gender-Linked Inherited Alcohol Addiction In Rodents ElucidatesHuman Condition

Not all mice are lushes. Most drink spirituous beverages inmoderation.

However, enough laboratory-bred rodents over-do their tipple ofethanol to make useful animal models for tracking the hereditarycomponent of alcoholism in humans.

One such mouse study, reported in the June issue of Nature Genetics,found that murine addiction traits differ by the sex of the animalstested. Molecular biologist Lee Silver at Princeton Universityfocused on two mouse strains with unusual inborn alcoholconsumption patterns.

B6 mice greedily guzzle large quantities of alcohol over long periods,in preference to food or water; DBA rodents never touch the stuff.Silver's team cross-bred the two types to monitor B6 genes that mightinfluence alcohol consumption.

They found one recessive alcohol-preference trait on murinechromosome 2; another on chromosome 11. The first acted only onmales; the second exclusively on females. This, they report, jibeswith human studies that have found separate genetic mechanisms inmen and women predisposed to alcohol abuse.

The Princetonian research also determined that genes that influencealcohol preference in their mice are unrelated to propensities forother forms of drug abuse, such as morphine predilection. "Why theB6 mouse has acquired independent preferences for multipleaddictive and euphoria-producing substances," the paper concluded,"remains a mystery."

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.