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

被引：43

作者：

Loomis, Rebecca J. ^{[1
]}

DiPiazza, Anthony T. ^{[1
]}

Falcone, Samantha ^{[2
]}

Ruckwardt, Tracy J. ^{[1
]}

Morabito, Kaitlyn M. ^{[1
]}

Abiona, Olubukola M. ^{[1
]}

Chang, Lauren A. ^{[1
]}

Caringal, Ria T. ^{[3
]}

Presnyak, Vladimir ^{[2
]}

Narayanan, Elisabeth ^{[2
]}

Tsybovsky, Yaroslav ^{[4
]}

Nair, Deepika ^{[1
]}

Hutchinson, Geoffrey B. ^{[1
]}

Stewart-Jones, Guillaume B. E. ^{[5
]}

Kueltzo, Lisa A.

Himansu, Sunny ^{[2
]}

Mascola, John R. ^{[5
]}

Carfi, Andrea ^{[2
]}

Graham, Barney S. ^{[1
]}

机构：

[1] NIAID, Natl Inst Hlth, Viral Pathogenesis Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA

[2] Moderna Inc, Cambridge, MA USA

[3] NIAID, Natl Inst Hlth, Vaccine Res Ctr, Vaccine Prod Program, Bethesda, MD 20892 USA

[4] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Vaccine Res Ctr Elect Microscopy Unit, Canc Res Technol Program, Frederick, MD USA

[5] NIAID, Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Vaccine Res Ctr,Virol Lab, Bethesda, MD 20892 USA

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷

基金：

美国国家卫生研究院;

关键词：

Nipah virus (NiV); mRNA; vaccine; Pre-F; G; structure-based immunogen design; pandemic preparedness and response; T cell responses; CRYO-EM STRUCTURE; HENDRA-VIRUS; HENIPAVIRUS INFECTION; MEMBRANE-FUSION; ANIMAL-MODELS; PIG-FARMERS; TRANSMISSION; ENCEPHALITIS; RECEPTOR; OUTBREAK;

D O I：

10.3389/fimmu.2021.772864

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：14

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