The University of California, Los Angeles, on Wednesdayinformed ID Biomedical Corp. (IDB), the exclusive licensee forUCLA's tuberculosis vaccine patent, that the vaccine hasdemonstrated protective immunity against Mycobacteriumtuberculosis in guinea pigs.
This event triggered payment of IDB's initial milestone toUCLA, which will be remitted to the university "within a 90-day period, starting today (Thursday)," said Frank Hollar,president of IDB of Vancouver, British Columbia.
Last April, UCLA selected IDB and its U.S. subsidiary, IDVaccine Corp., from a field of much larger applicant companiesfor a worldwide, exclusive license to commercialize its U.S.patent, "Tuberculosis and Legionellosis Vaccines, and Methodsfor Their Production" (No. 5,108,745 dated April 28, 1992),Frank Hollar's brother, Anthony, told BioWorld. Anthony Hollar,IDB's medical director, said the company could now make itsfirst milestone payment to UCLA under its tuberculosis vaccineagreement.
That milestone, Frank Hollar explained, "is the result ofdefining a pure protein vaccine, which demonstrated itsefficacy in the guinea pig model. This enables us to go forwardto primate studies."
These will begin this quarter as soon as the construction ofcages to house the test simians has been completed at thetesting facility, said Anthony Hollar. The toxicity and efficacytrials will be conducted in the Far East by the facility, whichspecializes in primate studies for companies and universitiesaround the world.
Guinea pigs are extremely sensitive to M. tuberculosis, whichmade them the animal models of choice for preliminaryevaluation of a TB vaccine, the medical director said. Likewise,the primates will have "fairly high susceptibility" to theinfection. Completion of these preclinical trials, expected beforethe end of the year, will trigger the second milestone paymentand lead to IDB submitting an investigational new drug (IND)application to the U.S. FDA either later this year or early next,Frank Hollar said. "So we may commence human trials in early1995."
"The guinea pig model is highly relevant to human tuberculosis,clinically, immunologically and pathologically," said UCLA'sMarcus Horwitz, the patent's sole inventor. "Therefore, we areoptimistic that this new vaccine will be as efficacious inhumans as it has been in guinea pigs."
It's not for lack of trying that no effective vaccine against TBhas ever reached clinical practice. Anthony Hollar explainedthat unlike most bacteria, mycobacteria break, enter and growinside the very macrophages designed by the immune systemto engulf, digest and destroy invading pathogens. M.tuberculosis is only one of a range of such intracellular bugsthat include the germs that cause Legionnaire's disease,leishmaniasis, toxoplasmosis and trachoma, among others.
Typically the macrophages digest these squatters, then presentvarious antigens to the cellular (lymphocytic) immune systemto get protection. Instead, mycobacteria hijack the macrophagesand kill them. In turn, other macrophages engulf and eat uptheir detritus, thus perpetuating the infection.
"That's why the immune system has such a problem with thesebugs," said Anthony Hollar. "Its T cells don't get a good view ofthe antigens they're supposed to pick up in order to destroythe invading bugs."
IDB and inventor Horwitz aim to give those T cells a betterview. Their vaccine's antigens are based on the 50 or morevaried extracellular proteins, identified by Horwitz, that M.tuberculosis secretes beyond its own wall into the macrophage.Most people, Hollar observed, have a built-in genetic resistanceto TB. "Those proteins secreted by the bugs do get presented inall likelihood to the immune system, and that's how peopledevelop immunity -- if it doesn't kill them first."
For its vaccine, IDB has purified a selected panel of thoseextracellular proteins from M. tuberculosis culture, which offerT cells more of a bull's-eye target in its prototype vaccine. "Inongoing work we have an initiative toward cloning all theseproteins," Hollar said.
So far, in guinea pigs (and soon in simians), the vaccine isadministered as a single-dose, subcutaneous injection.
"We know of no other TB vaccine that has an issued patent orpublished studies demonstrating protective immunity,"declared IDB's Frank Hollar. "So we believe ourselves to be inthe lead position worldwide."
IDB, which said it has about $7 million (Canadian) in the bankfrom an IPO in March 1992 and a second offering in the springof 1993, does not contemplate seeking investment capital inthe near future.
"We think that in North America TB will be a terrible problemin the next 10 years," said Anthony Hollar. "The public healthauthorities and the medical community aren't doing enough tocontrol this epidemic."
There are about 8 million new TB cases worldwide every year,with 3 million people dying of the disease. It is the largestcause of death in the world from a single infectious pathogen.In the U.S. there were 28,000 cases in 1992. TB also accountsfor 40 percent of all AIDS fatalities, according to one expert(see BioWorld, May 7, 1993).
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.