Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.
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.
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Norbert
N
Pardi
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Michael J
MJ
Hogan
Viral Pathogenesis Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rebecca S
RS
Pelc
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Hiromi
H
Muramatsu
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
Hanne
H
Andersen
Viral Pathogenesis Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Christina R
CR
DeMaso
Viral Pathogenesis Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kimberly A
KA
Dowd
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Laura L
LL
Sutherland
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Richard M
RM
Scearce
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Robert
R
Parks
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
Wendeline
W
Wagner
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
Alex
A
Granados
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
Jack
J
Greenhouse
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
Michelle
M
Walker
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Elinor
E
Willis
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Jae-Sung
JS
Yu
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Charles E
CE
McGee
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Gregory D
GD
Sempowski
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
Barbara L
BL
Mui
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
Ying K
YK
Tam
Diagnostic Medicine and Pathobiology, College of Veterinary Medicine and the Biosecurity Research Institute, Kansas State University, Manhattan, Kansas 66506, USA.
Yan-Jang
YJ
Huang
Diagnostic Medicine and Pathobiology, College of Veterinary Medicine and the Biosecurity Research Institute, Kansas State University, Manhattan, Kansas 66506, USA.
Dana
D
Vanlandingham
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Veronica M
VM
Holmes
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA.
Harikrishnan
H
Balachandran
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA.
Sujata
S
Sahu
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA.
Michelle
M
Lifton
Diagnostic Medicine and Pathobiology, College of Veterinary Medicine and the Biosecurity Research Institute, Kansas State University, Manhattan, Kansas 66506, USA.
Stephen
S
Higgs
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Scott E
SE
Hensley
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
Thomas D
TD
Madden
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
Michael J
MJ
Hope
BioNTech RNA Pharmaceuticals, An der Goldgrube 12, 55131 Mainz, Germany.
Katalin
K
Karikó
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA.
Sampa
S
Santra
Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Barney S
BS
Graham
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
Mark G
MG
Lewis
Viral Pathogenesis Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Theodore C
TC
Pierson
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Barton F
BF
Haynes
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Drew
D
Weissman
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007271:Injections, Intradermal; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D020871:RNA Stability; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D012367:RNA, Viral / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D013997:Time Factors; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000071244:Zika Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000071243:Zika Virus Infection / Q000276:immunology / Q000517:prevention & control*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D014765:Viral Vaccines