Author:
Kar Uddipan,Garg Priyanka,Khaleeq Sara,Vignesh Venkada Subramanian,Upadhyaya Aditya,Das Mili,Pandey Suman,Dutta Somnath,Varadarajan Raghavan
Abstract
AbstractInfluenza is a highly contagious virus, belonging to the family Orthomyxovirus that causes acute febrile respiratory illness which may even be fatal in some cases. Self-assembling protein nanoparticles have been used to display several copies of an immunogen, thus enhancing B cell and T cell immune responses through avidity effects. Using an iterative structure-guided approach, we successfully displayed twelve copies of a previously designed influenza stem domain immunogen pH1HA10 on the ferritin like protein, Msdps2. The nanoparticle fusion immunogen was well folded and bound to the influenza stem directed broadly neutralizing antibody CR6261 with very high affinity. An 8.5 angstrom Cryo-EM map of the nanoparticle fusion protein confirmed the successful design of the nanoparticle fusion immunogen. Preliminary mice immunization studies with the nanoparticle fusion construct revealed that the Msdps2-pH1HA10 fusion construct is immunogenic, this will be further evaluated in challenge studies.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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