Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic and protective in rodent models of RSV infection.

NPJ Vaccines
Amy S EspesethAndrew J Bett

Abstract

The RSV Fusion (F) protein is a target for neutralizing antibody responses and is a focus for vaccine discovery; however, the process of RSV entry requires F to adopt a metastable prefusion form and transition to a more stable postfusion form, which displays less potent neutralizing epitopes. mRNA vaccines encode antigens that are translated by host cells following vaccination, which may allow conformational transitions similar to those observed during natural infection to occur. Here we evaluate a panel of chemically modified mRNA vaccines expressing different forms of the RSV F protein, including secreted, membrane associated, prefusion-stabilized, and non-stabilized structures, for conformation, immunogenicity, protection, and safety in rodent models. Vaccination with mRNA encoding native RSV F elicited antibody responses to both prefusion- and postfusion-specific epitopes, suggesting that this antigen may adopt both conformations in vivo. Incorporating prefusion stabilizing mutations further shifts the immune response toward prefusion-specific epitopes, but does not impact neutralizing antibody titer. mRNA vaccine candidates expressing either prefusion stabilized or native forms of RSV F protein elicit robust neutralizing a...Continue Reading

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Citations

Aug 15, 2020·Frontiers in Immunology·Lea Skak Filtenborg FrederiksenAneesh Thakur
Sep 7, 2020·Journal of Nanobiotechnology·Estefânia V R CamposLeonardo Fernandes Fraceto
Aug 4, 2020·Antiviral Chemistry & Chemotherapy·Elena Margret ThornhillDavid Verhoeven
Sep 26, 2020·Frontiers in Immunology·Sana O AlturkiElias K Haddad
Dec 29, 2020·Advanced Drug Delivery Reviews·Jee Young ChungYoung Jik Kwon
Jan 19, 2021·Advanced Healthcare Materials·William HoXiaoyang Xu
Jan 6, 2021·Advanced Drug Delivery Reviews·Jeonghwan KimGaurav Sahay
Jan 23, 2021·Vaccines·Alberto Cagigi, Karin Loré
Jan 6, 2021·Pharmaceutics·Iman M AlfagihMariyam M Alfagih
Jan 11, 2021·Advanced Drug Delivery Reviews·Deborah PushparajahRoderick A Slavcev
Dec 8, 2020·Veterinary World·S N YadavM K Kalita

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Methods Mentioned

BETA
transfection
flow cytometry
ELISA
PCA
ELISAs
in vitro transcription
FACS
AlphaLISA
PCR

Software Mentioned

GraphPad Prism®
iQ5
ForteBio Data Analysis
GraphPad Prism
Moderna
Graph Pad Prism
FlowJo

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