1. Immunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA
- Author
-
Heinrich Haas, R. Levai, Roger Le Grand, Yoann Aldon, Annette B. Vogel, Robin J. Shattock, Ugur Sahin, Katalin Fábián, Nathalie Dereuddre-Bosquet, Jorge Moreno Herrero, Paul F. McKay, Pauline Maisonnasse, and Commission of the European Communities
- Subjects
Research & Experimental Medicine ,0601 Biochemistry and Cell Biology ,medicine.disease_cause ,Immunoglobulin G ,NONVIRAL DELIVERY ,0302 clinical medicine ,vaccine ,Drug Discovery ,chemistry.chemical_classification ,0303 health sciences ,biology ,IMMUNE-RESPONSES ,Chemistry ,Immunogenicity ,macaque ,3. Good health ,Medicine, Research & Experimental ,030220 oncology & carcinogenesis ,Molecular Medicine ,Original Article ,ELECTROPORATION ,Life Sciences & Biomedicine ,Env ,Transgene ,RM1-950 ,Semliki Forest virus ,NEUTRALIZING ANTIBODIES ,03 medical and health sciences ,Immune system ,medicine ,TYPE-1 ENVELOPE ,mouse ,030304 developmental biology ,Science & Technology ,EQUINE ENCEPHALITIS-VIRUS ,HIV ,polyplexes ,1103 Clinical Sciences ,IN-VITRO ,biology.organism_classification ,DNA VACCINE ,Virology ,PEI ,Venezuelan equine encephalitis virus ,T-CELLS ,biology.protein ,Therapeutics. Pharmacology ,CHALLENGE ,Glycoprotein ,saRNA - 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 (PLXs), 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 immunoglobulin G (IgG)2a 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., Graphical abstract, Aldon, McKay, and colleagues evaluated the potential of formulated VEEV and SFV self-amplifying mRNA (saRNA) for the delivery of HIV-1 Env stabilized trimers. The authors demonstrate great potential for PEI-polyplex formulated VEEV-saRNA platform, which elicits strong humoral responses at low doses in non-human primates.
- Published
- 2021
- Full Text
- View/download PDF