BCG, the classic tuberculosis vaccine, has found a new role asa delivery system for recombinant protein vaccines.
Two independent groups report in today's issue of Nature thatBCG bacteria that express HIV (the AIDS virus) subunitvaccines stimulate both antibody and cellular immuneresponses in mice.
BCG, or bacille Calmette-Guerin, is a live, inactivatedtuberculosis bacterium that has been safely administered to2.5 billion people. Due to its immunostimulatory properties,BCG has also been mixed with various vaccines to boost thebody's immune response to inoculation.
BCG vaccines are economic and heat-stable. They can bemodified for oral administration. In addition, since BCG livesin the body, it can continue to express a vaccine antigen formany years.
Several years ago, Dr. Barry Bloom of the Albert EinsteinCollege of Medicine in New York proposed using BCG as a hostfor recombinant-derived vaccines. However, "it was aformidable project to genetically engineer BCG," Bloom toldBioWorld. His laboratory ultimately designed the firstgeneration of BCG vectors in the late 1980s.
Now two groups using those vectors as a starting point haveshown that BCG can deliver recombinant protein vaccines andprovoke appropriate immune responses.
Researchers at Medimmune Inc. and the University ofPittsburgh worked with Bloom and his colleagues to developefficient systems to introduce vaccine-encoding genes intoBCG. Medimmune scientists have expressed 20 bacterial, viral,parasite and tumor antigens in BCG.
These include proteins from HIV, tetanus, malaria, rotavirus,streptococcus and toxoplasma, said Ken Stover, leader of theBCG Vaccine Project and lead author of the Nature paper thatreports that BCG-HIV and BCG-tetanus vaccines provokedcellular and antibody immune responses.
Anna Aldovini and Richard A. Young at the MassachusettsInstitute of Technology used a different expression system todevelop BCG-HIV vaccines. Their report in Nature also showsthat the vaccines provoked immune responses in mice.
Researchers still do not know whether the immune responseprovoked by bacteria-produced mammalian vaccines willrecognize the native mammalian protein. It's also not knownwhether people already inoculated with BCG will mount animmune response that destroys recombinant BCG vaccinesbefore they are able to work. Stover said that recombinantvaccines may be protected since BCG is sequestered insidemacrophage cells and the antibodies must attack from outside.
Gaithersburg, Md.-based Medimmune owns the technology toproduce recombinant vaccines using BCG, said Stover. Thecompany licensed technology from Einstein and MIT, in additionto filing patent applications on more recent developments.Medimmune has licensed BCG for the development of HIVvaccines to Merck and is working with Connaught Labs todevelop other BCG-based vaccines. Bloom is a member of thecompany's scientific advisory board.
Medimmune's (NASDAQ: MEDI) stock closed unchangedWednesday at $11.75.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.