Details

Autor(en) / Beteiligte

• Loomis, Rebecca J
• DiPiazza, Anthony T
• Falcone, Samantha
• Ruckwardt, Tracy J
• Morabito, Kaitlyn M
• Abiona, Olubukola M
• Chang, Lauren A
• Caringal, Ria T
• Presnyak, Vladimir
• Narayanan, Elisabeth
• Tsybovsky, Yaroslav
• Nair, Deepika
• Hutchinson, Geoffrey B
• Stewart-Jones, Guillaume B E
• Kueltzo, Lisa A
• Himansu, Sunny
• Mascola, John R
• Carfi, Andrea
• Graham, Barney S

Titel

Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen Delivery by mRNA as a Candidate Nipah Vaccine

Ist Teil von

• Frontiers in immunology, 2021-12, Vol.12, p.772864

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Nipah virus (NiV) represents a significant pandemic threat with zoonotic transmission from bats-to-humans with almost annual regional outbreaks characterized by documented human-to-human transmission and high fatality rates. Currently, no vaccine against NiV has been approved. Structure-based design and protein engineering principles were applied to stabilize the fusion (F) protein in its prefusion trimeric conformation (pre-F) to improve expression and increase immunogenicity. We covalently linked the stabilized pre-F through trimerization domains at the C-terminus to three attachment protein (G) monomers, forming a chimeric design. These studies detailed here focus on mRNA delivery of NiV immunogens in mice, assessment of mRNA immunogen-specific design elements and their effects on humoral and cellular immunogenicity. The pre-F/G chimera elicited a strong neutralizing antibody response and a superior NiV-specific Tfh and other effector T cell response compared to G alone across both the mRNA and protein platforms. These findings enabled final candidate selection of pre-F/G Fd for clinical development.