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

0549194 - BTÚ 2022 RIV US eng J - Journal Article
Kuchař, Milan - Kosztyu, P. - Daniel Lišková, Veronika - Černý, Jiří - Petroková, Hana - Vroblova, E. - Malý, Michal - Vaňková, Lucie - Krupka, M. - Raskova Kafkova, L. - Turánek Knotigová, P. - Dušková, Jarmila - Dohnálek, Jan - Mašek, J. - Turánek, J. - Raška, M. - Malý, Petr
Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice.
Virulence. Roč. 12, č. 1 (2021), s. 1271-1287. ISSN 2150-5594. E-ISSN 2150-5608
R&D Projects: GA MZd(CZ) NV15-32198A; GA MŠMT(CZ) EF16_025/0007397
Institutional support: RVO:86652036
Keywords : protein scaffold * combinatorial library * protein mimetics * Env glycoprotein
OECD category: Infectious Diseases
Impact factor: 5.428, year: 2021
Method of publishing: Open access
https://www.tandfonline.com/doi/full/10.1080/21505594.2021.1920251

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.
Permanent Link: http://hdl.handle.net/11104/0325214