Development of a potent Zika virus vaccine using self-amplifying messenger RNA
Kate Luisi, Kaitlyn M. Morabito, Katherine E. Burgomaster, Mayuri Sharma, Wing‐Pui Kong, Bryant M. Foreman, Sonal Patel, Brian E. Fisher, Maya Aleshnick, Jason P. Laliberte, Madison Wallace, Tracy J. Ruckwardt, David N. Gordon, Christine Linton, Nicole Ruggiero, Jessica Cohen, Russell Johnson, Kunal Aggarwal, Sung‐Youl Ko, Eun Sung Yang, Rebecca S. Pelc, Kimberly A. Dowd, Derek T. O’Hagan, Jeffrey B. Ulmer, Sally Mossman, Anna Sambor, Edith Lepine, John R. Mascola, Theodore C. Pierson, Barney S. Graham, Dong Yü
Abstract
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.