hops in a random fashion, and it is not found in M. 
tuberculosis strains. Current work is under way to 
characterize IS 1096 genetically and use it as the 
source of a novel transposon for random mutagene- 
sis of mycobacteria. (The project described immedi- 
ately above was also supported by a grant from the 
National Institutes of Health.) 
Recombinant BCG Vaccines and Novel 
Vaccine Strategies 
BCG is an attenuated mutant of the bovine tuber- 
culosis bacillus that has been used as a vaccine 
against tuberculosis in humans for over 50 years. 
This bacterium possesses several unique properties 
that make it an ideal candidate for use as a live vac- 
cine vector for generating multivalent vaccines. It is 
proven safe, having been used in 2.5 billion individ- 
uals with a significantly lower mortality rate than 
smallpox vaccine. Currently it is the only live vac- 
cine other than oral polio that is recommended by 
the World Health Organization to be given at birth. 
Also, the mycobacterial cell wall possesses potent 
adjuvant properties that can engender excellent hu- 
moral responses. In addition, since BCG normally 
resides within macrophages that are key antigen- 
presenting cells, it follows that it can elicit cellular 
immune responses to associated antigens. 
In the past few years. Dr. Jacobs' laboratory, in 
collaboration with Drs. Barry Bloom (HHMI, Albert 
Einstein College of Medicine), Graham F. HatfuU 
(University of Pittsburgh), and C. Kendall Stover 
(Medlmmune) , has developed a series of expression 
vectors and transformation systems that make it pos- 
sible to clone and express in BCG antigen-encoding 
foreign genes from virtually any pathogen. Mice im- 
munized with these recombinant BCG cells express- 
ing foreign antigens have been shown to elicit both 
humoral and cellular immune responses to the ex- 
pressed foreign proteins. 
To investigate the immune responses to foreign 
proteins expressed by BCG, Dr. Jacobs' laboratory is 
currently cloning and expressing genes from organ- 
isms that cause leishmaniasis, schistosomiasis, filari- 
asis, and toxoplasmosis. Such analyses should pro- 
vide the basic knowledge needed to engineer a 
recombinant BCG that could protect humans from 
these dread diseases. 
A grant from the National Institutes of Health pro- 
vided partial support for the work described above. 
Dr. Jacobs is also Associate Professor in the De- 
partments of Microbiology and Immunology and 
of Molecular Genetics at Albert Einstein College of 
Medicine of Yeshiva University, Bronx. 
Articles 
Barletta, R.G., Kim, D.D., Snapper, S.B., Bloom, 
B.R., and Jacobs, W.R., Jr. 1992. Identification 
of expression signals of the mycobacteriophages 
Bxbl, LI and TM4 using the Escherichia- 
Mycobacterium shuttle plasmids pYUB75 and 
pYUB76 designed to create translational fusions 
to the lacZ gciwc. J Gen Microbiol 138:23-30. 
Belisle, J.T., Pascopella, L., Inamine, J.M., Brennan, 
PJ., and Jacobs, W.R., Jr. 1991. Isolation and 
expression of a gene cluster responsible for bio- 
synthesis of the glycopeptidolipid antigens of 
Mycobacterium avium. J Bacteriol 173:6991- 
6997. 
Cirillo, J.D., Barletta, R.G., Bloom, B.R., and Ja- 
cobs, W.R., Jr. 1 99 1 . A novel transposon trap for 
mycobacteria: isolation and characterization of 
IS1096. J Bacteriol 173:7772-7780. 
Connell, N., Stover, K., and Jacobs, W.R., Jr. 1992. 
Old microbes with new faces: molecular biology 
and design of new vaccines. Curr Opin Immunol 
4:442-448. 
Daley, C.L., Small, P.M., Schecter, G.F., School- 
nik, O.K., McAdam, R.A., Jacobs, W.R., Jr., and 
Hopewell, P.C. 1992. An outbreak of tuberculosis 
with accelerated progression among persons in- 
fected with the human immunodeficiency virus. 
An analysis using restriction-fragment-length poly- 
morphisms. N Engl J Med 326:231-235. 
Jacobs, W.R., Jr. 1992. Advances in mycobacterial 
genetics: new promises for old diseases. Immuno- 
biology 184:147-156. 
Jacobs, W.R., Jr., Kalpana, G.V., Cirillo, J. D., Pas- 
copella, L., Snapper, S.B., Udani, R.A., Jones, W., 
Jr., Barletta, R.G., and Bloom, B.R. 1991 . Genetic 
systems for mycobacteria. Methods Enzymol 
204:537-555. 
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