Immunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA
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Published version
Author(s)
Type
Journal Article
Abstract
Self-amplifying mRNA (saRNA) represents a promising platform for nucleic acid delivery of vaccine immunogens. Unlike plasmid DNA, saRNA does not require entry into the nucleus of target cells for expression having the capacity to drive higher protein expression compared to mRNA as it replicates within the cytoplasm. In this study, we examined the potential of stabilized native-like HIV-1 Envelope glycoprotein (Env) trimers to elicit immune responses when delivered by saRNA polyplexes (PLX), assembled with linear polyethylenimine. We showed that Venezuelan equine encephalitis virus (VEEV) saRNA induces a stronger humoral immune response to the encoded transgene compared to Semliki Forest virus saRNA. Moreover, we characterized the immunogenicity of the soluble and membrane-bound ConSOSL.UFO Env design in mice and showed a faster humoral kinetic and an IgG2a skew using a membrane-bound design. The immune response generated by PLX VEEV saRNA encoding the membrane-bound Env was then evaluated in larger animal models including macaques in which low doses induced high IgG responses. Our data demonstrated that the VEEV saRNA PLX nanoparticle formulation represents a suitable platform for the delivery of stabilized HIV-1 Env and has the potential to be used in a variety of vaccine regimens.
Date Issued
2021-09-03
Date Acceptance
2021-06-16
Citation
Molecular Therapy - Nucleic Acids, 2021, 25, pp.483-493
ISSN
2162-2531
Publisher
Elsevier BV
Start Page
483
End Page
493
Journal / Book Title
Molecular Therapy - Nucleic Acids
Volume
25
Copyright Statement
© 2021 The Authors. This work is published under CC BY-NC-ND license.
Sponsor
Commission of the European Communities
Identifier
https://www.sciencedirect.com/science/article/pii/S2162253121001499?via%3Dihub
Grant Number
681137
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
EQUINE ENCEPHALITIS-VIRUS
DNA VACCINE
NONVIRAL DELIVERY
IMMUNE-RESPONSES
TYPE-1 ENVELOPE
NEUTRALIZING ANTIBODIES
IN-VITRO
T-CELLS
ELECTROPORATION
CHALLENGE
Env
HIV
PEI
macaque
mouse
polyplexes
saRNA
vaccine
0601 Biochemistry and Cell Biology
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2021-06-24