Efficacy of an inactivated Zika vaccine against virus infection during pregnancy in mice and marmosets

In-Jeong Kim; Paula A Lanthier; Madeline J Clark; Rafael A De La Barrera; Michael P Tighe; Frank M Szaba; Kelsey L Travis; Timothy C Low-Beer; Tres S Cookenham; Kathleen G Lanzer; Derek T Bernacki; Lawrence L Johnson; Amanda A Schneck; Corinna N Ross; Suzette D Tardif; Donna Layne-Colon; Stephanie D Mdaki; Edward J Dick Jr; Colin Chuba; Olga Gonzalez; Kathleen M Brasky; John Dutton; Julienne N Rutherford; Lark L Coffey; Anil Singapuri; Claudia Sanchez San Martin; Charles Y Chiu; Stephen J Thomas; Kayvon Modjarrad; Jean L Patterson; Marcia A Blackman

doi:10.1038/s41541-021-00426-0

Efficacy of an inactivated Zika vaccine against virus infection during pregnancy in mice and marmosets

NPJ Vaccines. 2022 Jan 27;7(1):9. doi: 10.1038/s41541-021-00426-0.

Authors

In-Jeong Kim¹, Paula A Lanthier², Madeline J Clark², Rafael A De La Barrera³, Michael P Tighe², Frank M Szaba², Kelsey L Travis², Timothy C Low-Beer², Tres S Cookenham², Kathleen G Lanzer², Derek T Bernacki², Lawrence L Johnson², Amanda A Schneck², Corinna N Ross⁴, Suzette D Tardif⁴, Donna Layne-Colon⁴, Stephanie D Mdaki⁴, Edward J Dick Jr⁴, Colin Chuba⁴, Olga Gonzalez⁴, Kathleen M Brasky⁴, John Dutton⁴, Julienne N Rutherford⁵, Lark L Coffey⁶, Anil Singapuri⁶, Claudia Sanchez San Martin^{7

8}, Charles Y Chiu⁷, Stephen J Thomas⁹, Kayvon Modjarrad¹⁰, Jean L Patterson¹¹, Marcia A Blackman¹²

Affiliations

¹ Trudeau Institute, Inc., Saranac Lake, NY, 12983, USA. ijkim@trudeauinstitute.org.
² Trudeau Institute, Inc., Saranac Lake, NY, 12983, USA.
³ Pilot Bioproduction Facility, Center for Enabling Capabilities, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.
⁴ Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA.
⁵ Department of Human Development Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, IL, 60612, USA.
⁶ Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
⁷ Department of Laboratory Medicine, School of Medicine, University of California at San Francisco, San Francisco, CA, 94158, USA.
⁸ Division of Infectious Diseases and Vaccinology, School of Public Health, University of California at Berkeley, Berkeley, CA, 94720, USA.
⁹ Division of Infectious Diseases, Institute for Global Health and Translational Sciences, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA.
¹⁰ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.
¹¹ Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. jpatters@txbiomed.org.
¹² Trudeau Institute, Inc., Saranac Lake, NY, 12983, USA. mblackman@trudeauinstitute.org.

Abstract

Zika virus (ZIKV) is a mosquito-borne arbovirus that can cause severe congenital birth defects. The utmost goal of ZIKV vaccines is to prevent both maternal-fetal infection and congenital Zika syndrome. A Zika purified inactivated virus (ZPIV) was previously shown to be protective in non-pregnant mice and rhesus macaques. In this study, we further examined the efficacy of ZPIV against ZIKV infection during pregnancy in immunocompetent C57BL6 mice and common marmoset monkeys (Callithrix jacchus). We showed that, in C57BL/6 mice, ZPIV significantly reduced ZIKV-induced fetal malformations. Protection of fetuses was positively correlated with virus-neutralizing antibody levels. In marmosets, the vaccine prevented vertical transmission of ZIKV and elicited neutralizing antibodies that remained above a previously determined threshold of protection for up to 18 months. These proof-of-concept studies demonstrate ZPIV's protective efficacy is both potent and durable and has the potential to prevent the harmful consequence of ZIKV infection during pregnancy.

Abstract

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