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1.
Bioorg Khim ; 34(5): 639-44, 2008.
Article in Russian | MEDLINE | ID: mdl-19060938

ABSTRACT

We and other authors have recently shown that the pattern of the immune response to components of anthrax, the Bacillus anthracis lethal toxin, is complex. In addition to neutralizing antibodies, the antitoxin antibody pool contains antibodies enhancing the toxin lethal action. We mapped the epitopes in the protective antigen that are responsible for the induction of both antibody types. In this study, we obtained new data on the cytotoxicity of the B. anthracis lethal toxin toward the J774 A.1 cell line in the presence of monoclonal antibodies to various domains of the protective antigen and the lethal factor. The role of the Fc fragment of immunoglobulins in enhancing the lethal toxin action was shown. These results may serve as a basis for the development of a new generation vaccine for anthrax.


Subject(s)
Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Bacillus anthracis/immunology , Bacterial Toxins/immunology , Exotoxins/immunology , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Cell Line , Epitope Mapping , Immunoglobulin Fc Fragments/immunology , Mice
3.
Mol Gen Mikrobiol Virusol ; (1): 3-7, 2005.
Article in Russian | MEDLINE | ID: mdl-15790026

ABSTRACT

Above two million people annually die worldwide of tuberculosis. There has been a serious uptrend in the tuberculosis morbidity observed during the recent decade in Russia. The growing prevalence of drug-resistant strains of pathogens is highly dangerous. A timely diagnosis reduces significantly the risk of epidemics. The use of molecular methods cuts the time of tuberculosis diagnosis, including its resistant forms, from several weeks to several days. The presented survey contains a discussion of modem methods used for identification of Mycobacterium tuberculosis resistance to the main anti-TB drugs.


Subject(s)
Antitubercular Agents/pharmacology , Drug Resistance, Bacterial/genetics , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Alleles , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Humans , Mutation , Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Hybridization , Polymerase Chain Reaction , Sequence Analysis , Tuberculosis/drug therapy
4.
Mol Gen Mikrobiol Virusol ; (3): 21-6, 2004.
Article in Russian | MEDLINE | ID: mdl-15354937

ABSTRACT

Anthrax belongs to highly dangerous infections of man and animals. No effective treatment methods for pulmonary types of the disease have been yet developed. The existing anthrax vaccines were designed decades ago and need improvement to fit the large-scale vaccination of population. At the same time, the immunological properties of the anthrax vaccine main component, i.e. of the protective agent, have been poorly studied. We obtained, within the present case study, a panel of mouse monoclonal antibodies to the protective agent and investigated the properties of the highest-affine panel representatives. An unusual phenomenon was detected, which is related with enhancement of the anthrax toxin action on the mouse macrophage-like cell-line in presence of the 1F2 monoclonal antibody. The remaining analyzed antibodies, i.e. 6G8 and 6G7, were found to neutralize effectively the toxin action. The enhancing and neutralizing antibodies were proven to be specific to different domains of the protective antigen and to recognize epitopes in its composition. The antibody-mediated enhancement of the anthrax lethal action is a convincing argument for further development of a new-generation anthrax vaccine. Definition of the linear antigen determinants for neutralizing antibodies in the protective antigens is an important step in the development of the next-generation anthrax vaccine.


Subject(s)
Anthrax Vaccines/immunology , Antibodies, Monoclonal/immunology , Antigens, Bacterial/immunology , Bacillus anthracis , Bacterial Toxins/immunology , Animals , Anthrax Vaccines/pharmacology , Antibodies, Bacterial/immunology , Antigens, Bacterial/pharmacology , Bacterial Toxins/pharmacology , Cell Line , Epitopes/immunology , Macrophages/virology , Mice , Mice, Inbred BALB C , Neutralization Tests
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