Immunological properties of synthetic peptides that copy V3 loop region of the HIV-1 gp120 envelope protein with various method of administration and poly (I:C) immunoadjvant use

Synthetic peptides are a good basis for HIV vaccine development.  The immune response are focused only on a specific epitope after their administration, they are able to activate both pathways (humoral and cellular) of the immune response, and they are safe and well tolerated. Having a low molecular weight, synthetic peptides possess a low immunogenicity, therefore it is necessary to use various immunoadjuvants in an immunogenic composition. V3 loops of the gp120 envelope  protein is one of the main protective epitope, and a number of monoclonal antibodies with broad neutralizing activity have been obtained to it. We conducted a study of the immunogenicity of peptides copying the V3 loop of the group M HIV1 virus consensus sequence and the Russian isolate RUA022a2. The impact of  the method of administration (subcutaneously and intraperitoneally) and the use of an immunoadjuvant was also assessed. A synthetic analogue of double-stranded RNA, poly (I:C) was used as an adjuvant. poly (I:C)  is a ligand of innate immunity receptors TLR3. The studies were conducted on balb/c mice. It has been shown that the method of administration does not affect an immune response development to the peptides. However, earlier production of specific IgG antibodies was observed in the groups where the immunoadjuvant was used. At the same time, the antibody titer was slightly higher in the groups where peptides were administered with the adjuvant after the third (last) administration. There were also no differences in the isotype of the induced antibodies. IgG1 antibodies were predominantly induced in all groups. Specific IgM antibodies were detected only after the third administration of the antigens. Their titer did not depend on the administration method and the antibody titer was slightly higher in the groups where peptides were administered with the poly (I:C).  The induced antibodies did not have neutralizing activity against isolate QF495.23.M.EnvA1. In the study of antigen-specific cellular activation the production of the marker of the Th1 response IFN γ is detected only in groups where poly(I:С) was used. In addition, a low level of anti-inflammatory cytokine IL10 was determined in groups where poly (I:С) was included in the immunogenic composition. In addition, the IL10 highest level was detected in groups with intraperitoneal administration. Studies have shown that the use of poly (I:С) adjuvant promotes the immune response development  to the synthetic peptides, that contributes to  earlier induction of specific antibodies, as well as switching to the Th1 pathway. The data obtained can be used in the design of HIV vaccines and other viral infections to increase their immunogenicity and the possibility of inducing a protective immune response.

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