Ad26.M.Env ZIKV vaccine protects pregnant rhesus macaques and fetuses against Zika virus infection

Amanda J Martinot; Freek Cox; Peter Abbink; Jonathan L Hecht; Roderick Bronson; Erica N Borducchi; William J Rinaldi; Melissa J Ferguson; Rafael A De La Barrera; Roland Zahn; Leslie van der Fits; Dan H Barouch

doi:10.1038/s41541-024-00927-8

Ad26.M.Env ZIKV vaccine protects pregnant rhesus macaques and fetuses against Zika virus infection

NPJ Vaccines. 2024 Aug 28;9(1):157. doi: 10.1038/s41541-024-00927-8.

Authors

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. amanda.martinot@tufts.edu.
² Departments of Infectious Disease and Global Health and Comparative Pathobiology, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. amanda.martinot@tufts.edu.
³ Janssen Vaccines & Prevention, Leiden, the Netherlands.
⁴ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Division of Anatomic Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁶ Harvard Medical School, Boston, MA, USA.
⁷ Alphagenesis, Yemassee, SC Alphagenesis, Yemassee, SC, USA.
⁸ Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. dbarouch@bidmc.harvard.edu.
¹⁰ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. dbarouch@bidmc.harvard.edu.

Abstract

At the start of the Zika virus (ZIKV) epidemic in 2015, ZIKV spread across South and Central America, and reached parts of the southern United States placing pregnant women at risk for fetal microcephaly, fetal loss, and other adverse pregnancy outcomes associated with congenital ZIKA syndrome (CZS). For this reason, testing of a safe and efficacious ZIKV vaccine remains a global health priority. Here we report that a single immunization with Ad26.M.Env ZIKV vaccine, when administered prior to conception, fully protects pregnant rhesus macaques from ZIKV viral RNA in blood and tissues with no adverse effects in dams and fetuses. Furthermore, vaccination prevents ZIKV distribution to fetal tissues including the brain. ZIKV associated neuropathology was absent in offspring of Ad26.M.Env vaccinated dams, although pathology was limited in fetuses from non-immunized, challenged dams. Vaccine efficacy is associated with induction of ZIKV neutralizing antibodies in pregnant rhesus macaques. These data suggest the feasibility of vaccine prevention of CZS in humans.

Grants and funding

K08 135098-01A1/Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)