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IMMUNOLOGICAL CHARACTERISTIC OF SYNTHETIC PEPTIDES SIMILAR TO ACTUAL HIV ANTIGEN DETERMINANTS

https://doi.org/10.15789/1563-0625-2016-1-51-62

Abstract

The development of HIV vaccine remains an important goal in prophylaxis and therapy of HIV/ AIDS epidemics. There are various approaches for development of а candidate vaccine based on induction of neutralizing antibodies and cell-mediated immunity. Synthetic peptides are considered promising vaccine antigens since they are capable of activating both humoral and cellular immune response. HIV-1 envelope gp120 is the target for neutralizing antiviral antibodies. The V3 region of the HIV-1 gp120 is highly immunogenic and important for the virus-coreceptor interaction. In a RV144 vaccine trial, the levels of vaccine-induced IgG antibodies recognizing V1V2 regions from multiple HIV-1 subtypes show inverse correlations with a risk for HIV-1 infection. Meanwhile, HIV is characterized by high diversity. The consensus and mosaic immunogens are complete but artificial proteins, which are computationally designed to elicit immune responses with improved cross-reactive broadness. We have been studied immunogenic properties of synthetic peptides derived from V1, V2, V3 loop regions of the consensus M HIV1 (CON-S) sequence group of the gp 120 envelope protein and V3 loop derived from a Russian RUA022a2 isolate. These peptides specifically reacted to HIV-positive sera in ELISA, thus indicating their similarity to appropriate HIV proteins. The peptides proved to be weakly immunogenic. Therefore, Freund complete adjuvant was used to enhance peptide immunogenicity. To assess the immunogenicity, the mice were immunized with a peptide mixture. Antibodies have been developed to every peptide from the mixture, being, predominantly, of IgG isotype. The antibody titers depended on the length of peptide sequences. However, the sera from immunized mice did not have a HIV neutralizing activity. The serum neutralization was assessed by pseudovirus-based assay, using a molecular clone of virus isolates CAP 45.2.00.G3 and QH.209.14.M.EnvA2. The virus neutralization is a complex process and may be influenced by several factors, such as antibody titer, isotype, or antibody structure. Probably, to induce neutralizing antibodies by this peptide mixture, it is necessary to choose appropriate adjutants and immunization schedule. Moreover, it was shown that peptides could increase in vitro virus infectivity in pseudovirus-based model, using the CAP 45.2.00.G3, QH209.14M.ENV.A2, QD435.100M.ENV.E1 molecular clone. These viral isolates belong to different HIV-1 subtypes.

About the Authors

S. V. Korobova
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

PhD (Biology), Senior Research Associate, Laboratory of Polysaccharide Vaccines, Department of Immune Biotechnology,

115478, Moscow, Kashirskoye сh., 24, bldg 2



G. V. Kornilaeva
N.Gamaleya Research Institute of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation
Russian Federation

PhD (Biology), Leading Research Associate, Laboratory of Immunochemistry, Department of Molecular Virology,

Moscow



V. A. Toporova
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Russian Federation

Junior Research Associate, Laboratory of Protein Engineering, Department of Bioengineering,

Moscow



I. A. Nikolaeva
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

PhD, MD (Biology), Leading Research Associate, Department of Scientific Research Planning and Coordination,

Moscow



L. P. Trubcheninova
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

PhD (Biology), Head, Immune Disease Diagnosis Laboratory, Department of Immunodiagnosis and Immune Correction,

Moscow



N. F. Trefilyeva
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

Laboratory medical adviser, Immune Disease Diagnosis Laboratory, Department of Immunodiagnosis and Immune Correction,

Moscow



L. P. Sizyakina
Research Institute of Immunology, Rostov State Medical University
Russian Federation

PhD, MD (Medicine), Professor, Director,

Rostov-on-Don



I. G. Sidorovich
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

PhD, MD (Medicine), Professor, Chief Research Associate, Information and Analysis Department,

Moscow



P. G. Aparin
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

PhD, MD (Medicine), Head, Polysaccharide Vaccines Laboratory, Department of Immune Biotechnology,

Moscow



R. M. Khaitov
Institute of Immunology, Federal Medico-Biological Agency
Russian Federation

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Chief of Research,

Moscow



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For citations:


Korobova S.V., Kornilaeva G.V., Toporova V.A., Nikolaeva I.A., Trubcheninova L.P., Trefilyeva N.F., Sizyakina L.P., Sidorovich I.G., Aparin P.G., Khaitov R.M. IMMUNOLOGICAL CHARACTERISTIC OF SYNTHETIC PEPTIDES SIMILAR TO ACTUAL HIV ANTIGEN DETERMINANTS. Medical Immunology (Russia). 2016;18(1):51-62. (In Russ.) https://doi.org/10.15789/1563-0625-2016-1-51-62

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