Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.
Pardi Norbert, Hogan Michael J, Pelc Rebecca S, Muramatsu Hiromi, Andersen Hanne, DeMaso Christina R, Dowd Kimberly A, Sutherland Laura L, Scearce Richard M, Parks Robert, Wagner Wendeline, Granados Alex, Greenhouse Jack, Walker Michelle, Willis Elinor, Yu Jae-Sung, McGee Charles E, Sempowski Gregory D, Mui Barbara L, Tam Ying K, Huang Yan-Jang, Vanlandingham Dana, Holmes Veronica M, Balachandran Harikrishnan, Sahu Sujata, Lifton Michelle, Higgs Stephen, Hensley Scott E, Madden Thomas D, Hope Michael J, Karikó Katalin, Santra Sampa, Graham Barney S, Lewis Mark G, Pierson Theodore C, Haynes Barton F, Weissman Drew
Nature · 2017 · PMID 28151488 · 인용 894
Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority.
Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination.
These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.