Development of a potent Zika virus vaccine using self-amplifying messenger RNA

被引:63
作者
Luisi, Kate [1 ]
Morabito, Kaitlyn M. [2 ]
Burgomaster, Katherine E. [3 ]
Sharma, Mayuri [1 ,4 ]
Kong, Wing-Pui [2 ]
Foreman, Bryant M. [3 ]
Patel, Sonal [1 ]
Fisher, Brian [2 ]
Aleshnick, Maya A. [3 ,5 ]
Laliberte, Jason [1 ]
Wallace, Madison [1 ]
Ruckwardt, Tracy J. [2 ]
Gordon, David N. [3 ]
Linton, Christine [1 ,6 ]
Ruggiero, Nicole [1 ,7 ]
Cohen, Jessica L. [1 ]
Johnson, Russell [1 ]
Aggarwal, Kunal [1 ]
Ko, Sung-Youl [2 ]
Yang, Eun Sung [2 ]
Pelc, Rebecca S. [3 ,8 ]
Dowd, Kimberly A. [3 ]
O'Hagan, Derek [1 ]
Ulmer, Jeffrey [1 ]
Mossman, Sally [1 ]
Sambor, Anna [1 ]
Lepine, Edith [1 ,9 ]
Mascola, John R. [2 ]
Pierson, Theodore C. [3 ]
Graham, Barney S. [2 ]
Yu, Dong [1 ]
机构
[1] GSK Vaccines, Rockville, MD 20850 USA
[2] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] NIAID, Lab Viral Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[4] Takeda Pharmaceut, 35 Lansdowne St, Cambridge, MA USA
[5] Oregon Hlth & Sci Univ, 15700 SW Greystone Ct, Beaverton, OR 97006 USA
[6] Janssen Pharmaceut Co J&J, Spring House, PA USA
[7] Matrivax, 650 Albany St, Boston, MA USA
[8] North Carolina State Lab Publ Hlth, Raleigh, NC USA
[9] Vetoquinol, Lavaltrie, PQ, Canada
关键词
ANTIBODY-MEDIATED NEUTRALIZATION; DNA VACCINE; PROTECTIVE EFFICACY; NONVIRAL DELIVERY; HEALTHY-ADULTS; DENGUE VIRUS; PROTEINS; DETERMINANTS; ORGANIZATION; CHALLENGE;
D O I
10.1126/sciadv.aba5068
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Zika virus (ZIKV) is the cause of a pandemic associated with microcephaly in newborns and Guillain-Barre syndrome in adults. Currently, there are no available treatments or vaccines for ZIKV, and the development of a safe and effective vaccine is a high priority for many global health organizations. We describe the development of ZIKV vaccine candidates using the self-amplifying messenger RNA (SAM) platform technology delivered by cationic nanoemulsion (CNE) that allows bedside mixing and is particularly useful for rapid responses to pandemic outbreaks. Two immunizations of either of the two lead SAM (CNE) vaccine candidates elicited potent neutralizing antibody responses to ZIKV in mice and nonhuman primates. Both SAM (CNE) vaccines protected these animals from ZIKV challenge, with one candidate providing complete protection against ZIKV infection in nonhuman primates. The data provide a preclinical proof of concept that a SAM (CNE) vaccine candidate can rapidly elicit protective immunity against ZIKV.
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页数:10
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