Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice

Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction...

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Published in:	Molecular immunology Vol. 47; no. 1; pp. 87 - 95
Main Authors:	Durova, Oxana M., Vorobiev, Ivan I., Smirnov, Ivan V., Reshetnyak, Andrew V., Telegin, Georgy B., Shamborant, Olga G., Orlova, Nadezda A., Genkin, Dmitry D., Bacon, Andrew, Ponomarenko, Natalia A., Friboulet, Alain, Gabibov, Alexander G.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-11-2009 Elsevier
Subjects:	AIDS Vaccines - immunology Animal models Animals Antibodies, Catalytic - biosynthesis Antibodies, Monoclonal - biosynthesis Autoimmunity Capsid Proteins - immunology Capsid Proteins - therapeutic use Catalytic antibodies CD4 antigen Cell culture Chemical engineering Chemical Sciences Coats DNA vaccines Drug development EAE Epitopes Glycoprotein gp120 HIV Envelope Protein gp120 - immunology HIV-1 DNA/protein vaccine Human immunodeficiency virus 1 Immune system Immunization - methods Immunotherapy Infection Liposome delivery Liposomes Lymphocytes Mice Monoclonal antibodies Myelin basic protein Myelin Basic Protein - immunology Peptide Fragments - immunology Protein Engineering Proteolysis Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - therapeutic use SJL mice surface antigens Vaccination Vaccines Vaccines, DNA Autoimmunity HIV-1 DNA/protein vaccine EAE Catalytic antibodies SJL mice Liposome delivery
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Summary:	Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4 + receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production “catalytic vaccine”. Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0161-5890 1872-9142
DOI:	10.1016/j.molimm.2008.12.020