Development of an mRNA-lipid nanoparticle vaccine against Lyme disease

Lyme disease is the most common vector-borne infectious disease in the United States, in part because a vaccine against it is not currently available for humans. We propose utilizing the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform to generate a Lyme disease vaccine l...

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Bibliographic Details
Published in:Molecular therapy 2023-09, Vol.31 (9), p.2702-2714
Main Authors: Pine, Matthew, Arora, Gunjan, Hart, Thomas M., Bettini, Emily, Gaudette, Brian T., Muramatsu, Hiromi, Tombácz, István, Kambayashi, Taku, Tam, Ying K., Brisson, Dustin, Allman, David, Locci, Michela, Weissman, Drew, Fikrig, Erol, Pardi, Norbert
Format: Article
Language:English
Subjects:
Animals
antibody
antigen
Antigens, Surface - genetics
bacteria
Bacterial Outer Membrane Proteins - genetics
Borrelia burgdorferi
COVID-19 - prevention & control
COVID-19 Vaccines
Humans
lipid nanoparticle
Lyme disease
Lyme Disease - prevention & control
Mice
mRNA
nucleoside-modification
Original
OspA
SARS-CoV-2
spirochete
vaccine
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Summary:Lyme disease is the most common vector-borne infectious disease in the United States, in part because a vaccine against it is not currently available for humans. We propose utilizing the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform to generate a Lyme disease vaccine like the successful clinical vaccines against SARS-CoV-2. Of the antigens expressed by Borrelia burgdorferi, the causative agent of Lyme disease, outer surface protein A (OspA) is the most promising candidate for vaccine development. We have designed and synthesized an OspA-encoding mRNA-LNP vaccine and compared its immunogenicity and protective efficacy to an alum-adjuvanted OspA protein subunit vaccine. OspA mRNA-LNP induced superior humoral and cell-mediated immune responses in mice after a single immunization. These potent immune responses resulted in protection against bacterial infection. Our study demonstrates that highly efficient mRNA vaccines can be developed against bacterial targets. [Display omitted] Pardi and colleagues developed a nucleoside-modified mRNA vaccine against Lyme disease. The OspA-targeting vaccine induced robust T cell, germinal center B cell, memory B cell, long-lived plasma cell, and durable antibody responses in mice. Importantly, the vaccine induced a high level of protection from Borrelia burgdorferi infection after a single immunization.
ISSN:1525-0016
1525-0024
1525-0024
DOI:10.1016/j.ymthe.2023.07.022