Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the fi...

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Bibliographic Details
Published in:Journal of controlled release 2023-10, Vol.362, p.536-547
Main Authors: McCrudden, Cian M., Bennie, Lindsey, Chambers, Philip, Wilson, Jordan, Kerr, Megan, Ziminska, Monika, Douglas, Hayley, Kuhn, Sarah, Carroll, Emma, O'Brien, Garrett, Buckley, Niamh, Dunne, Nicholas J., McCarthy, Helen O.
Format: Article
Language:English
Subjects:
antibodies
encapsulation
Envelope antigen
Intradermal
lipids
Membrane antigen
mRNA
nanoparticles
Peptide
peptides
RALA
respiratory system
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Spike antigen
T-lymphocytes
vaccination
Vaccine
vaccines
weight loss
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Summary:Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust TH1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines. [Display omitted] •The RALA Peptide can deliver multiple mRNA in a nanoformulation.•The RALA/SME vaccine can be delivered intradermally or intramuscularly.•The RALA/SME vaccine induces both an antibody and T-cell response.•The RALA/SME vaccine exhibits no toxicities following vaccination.•The RALA/SME vaccine produces neutralising antibodies against SARS-CoV-2 variants.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2023.08.053