Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice

• Main Authors: Milan Kuchař, Petr Kosztyu, Veronika Daniel Lišková, Jiří Černý, Hana Petroková, Eliška Vróblová, Michal Malý, Lucie Vaňková, Michal Křupka, Leona Rašková Kafková, Pavlína Turánek Knotigová, Jarmila Dušková, Jan Dohnálek, Josef Mašek, Jaroslav Turánek, Milan Raška, Petr Malý
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Virulence
• Subjects: protein scaffold; protein mimetics; combinatorial library; env glycoprotein; broadly neutralizing antibody; hiv vaccine
• Online Access: http://dx.doi.org/10.1080/21505594.2021.1920251
• ISSN: 2150-5594; 2150-5608

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.