Development of an mRNA-lipid nanoparticle vaccine against Lyme disease
Matthew Pine, Gunjan Arora, Thomas Hart, Emily Bettini, Brian T. Gaudette, Hiromi Muramatsu, István Tombácz, Taku Kambayashi, Ying K. Tam, Dustin Brisson, David Allman, Michela Locci, Drew Weissman, Erol Fikrig, Norbert Pardi
Abstract
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.