CHIMERIC PROTEIN HBcAg CONTAINING THE EPITOPE MIMETIC RECOGNIZED BY MONOCLONAL ANTIBODY VRC01

The HIV-1 epidemic is one of the most acute problems of the modern healthcare. The discovery of broadly neutralizing antibodies (bnAbs) which possesses neutralizing activity against most primary isolates of HIV-1, has added an optimism to the vaccine researchers. According to several authors, the design of an immunogen capable of inducing such antibodies can provide protection against the wide genetic diversity of HIV-1 and thus contribute to the development of an effective vaccine against this virus. The aim of this work was the construction of an HIV-immunogen capable of inducing virus-neutralizing antibodies having the properties of bnAbs VRC01. This unique monoclonal antibody can neutralize about 91% of the different HIV-1 isolates. HBcAg is one of the promising systems for the presentation of foreign epitopes (peptides) for the development of highly immunogenic vaccines. In this work, HBcAg was used as a carrier of the SWTLLGY peptide (an epitope mimic recognized by the monoclonal antibody VRC01, previously selected using a phage display library). The recombinant plasmid pUC/HBcAg-mimicVRC01 was obtained; it contained the sequence HBcAg, with the inserted sequence encoding the SWTLLGY peptide in the region of the main antigenic determinant of the core. BALB/c mice were immunized with purified protein preparations. Using the ELISA it was shown that sera from immunized animals contained antibodies that specifically recognized the recombinant protein HBcAg-mimicVRC01. IgG fractions were isolated to assess the viral neutralizing activity from the sera of immunized animals. Neutralizing activity of IgGs was analyzed using the recombinant HIV-1 virus 92BR025. The results of neutralizing analysis showed that IgGs from sera of animals, immunized with HBcAg-mimicVRC01 protein, can neutralize the recombinant 92BR025 virus.