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

• 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
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2008.12.020

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.