One of the proposed strategies for the development of a more efficient HIV-1 vaccine is based on the identification of proteins binding to a paratope of chosen broadly neutralizing antibody (bNAb) that will mimic cognate HIV-1 Env (glyco)protein epitope and could be used as potent immunogens for induction of protective virus-neutralizing antibodies in the immunized individuals. To verify this "non-cognate ligand" concept, we developed a highly complex combinatorial library designed on a scaffold of human myomesin-1 protein domain and selected proteins called Myomedins specifically binding to variable regions of HIV-1 broadly neutralizing antibody 10E8. Immunization of mice with these Myomedin variants elicited the production of HIV-1 Env-specific antibodies. Hyperimmune sera bound to Env pseudotyped viruses and weakly/moderately neutralized 54% of tested clade A, B, C, and AE pseudotyped viruses variants in vitro. These results demonstrate that Myomedin variants have the potential to mimic Env epitopes and could be used as potential HIV-1 vaccine components.

Department of Immunology Palacký University Olomouc Olomouc Czech Republic

Department of Pharmacology and Immunotherapy Veterinary Research Institute Brno Czech Republic

Laboratory of Ligand Engineering Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Research Center Vestec Czech Republic

Laboratory of Structural Bioinformatics of Proteins Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Research Center Vestec Czech Republic

Laboratory of Structure and Function of Biomolecules Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Research Center Vestec Czech Republic

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