An optimized purified inactivated Zika vaccine provides sustained immunogenicity and protection in cynomolgus macaques

Valérie Lecouturier,Catherine Berry,Florence Boudet,Jon Heinrichs,Nicolas Jackson,Arnaud Donadieu,Aymeric De Montfort,Vincent Pavot,Bachra Rokbi

doi:10.1038/s41541-020-0167-8

Valérie Lecouturier, Catherine Berry + Show 7 more

Open Access

https://doi.org/10.1038/s41541-020-0167-8

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Journal: npj Vaccines	Publication Date: Mar 12, 2020
Citations: 17	License type: open-access

Affiliation: Sanofi (France), Sanofi (United States)

Abstract

The recent spread of Zika virus (ZIKV) through the Americas and Caribbean and its devastating consequences for pregnant women and their babies have driven the search for a safe and efficacious ZIKV vaccine. Among the vaccine candidates, a first-generation ZIKV purified inactivated vaccine (ZPIV), adjuvanted with aluminum hydroxide, developed by the Walter Reed Army Institute of Research (WRAIR), has elicited high seroconversion rates in participants in three phase-I clinical trials. In collaboration with the WRAIR, Sanofi Pasteur (SP) optimized the production scale, culture and purification conditions, and increased the regulatory compliance, both of which are critical for clinical development and licensure of this vaccine. Using a clinical batch of the first-generation ZPIV as a benchmark, we report that different doses of the optimized vaccine (ZPIV-SP) elicited sustained neutralizing antibodies, specific T- and memory B-cells, and provided complete protection against a ZIKV challenge in cynomolgus macaques. These data provide evidence that the ZPIV-SP vaccine performs at least as well as the ZPIV vaccine, and provide support for continued development in the event of future ZIKV outbreaks.

Highlights

After its discovery in Africa in 1947, Zika virus (ZIKV) was reported to be responsible for minor infections on the African continent and in South Asia[1]
Cynomolgus macaques were immunized with three-dose levels (100, 200, and 400 antigenic units, AU) of the optimized ZIKV purified inactivated vaccine (ZPIV)-Sanofi Pasteur (SP) in comparison to 200 AU of the first-generation ZPIV previously tested in human clinical studies (Fig. 1)
The MN50 titers were significantly higher at all time-points in macaques immunized with the ZPIV-SP 400 AU dose (P-value < 0.001) with a threefold mean increase compared with the other dose levels of ZPIV-SP (Fig. 2b and Supplementary Fig. 1)

Summary

Introduction

After its discovery in Africa in 1947, Zika virus (ZIKV) was reported to be responsible for minor infections on the African continent and in South Asia[1]. There have been reports of Guillain-Barré syndrome and other neurologic disorders following ZIKV infection in adults[4,5]. There has been a strong decline in new ZIKV infections in South and Central America, their serious impact on fetuses and infants and the extended distribution of ZIKV’s transmission vector, Aedes aegypti, maintain Zika as a public health concern[8]. The threat of future outbreaks is considered as a real risk, based on recent ZIKV infections reported in Asia[9,10,11]. Many organizations have undertaken the development of Zika vaccine candidates, using both traditional and more novel vaccine platform technologies[12,13]

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Results

Conclusion