Immunogenicity and protection conferred by an optimized purified inactivated Zika vaccine in mice.

Authors:
Marie-Clotilde Bernard
Marie-Clotilde Bernard
Freie Universität Berlin
Germany
Catherine Berry
Catherine Berry
University of Glasgow
United Kingdom
Eric Richier
Eric Richier
Liverpool School of Tropical Medicine
United Kingdom
Jon Heinrichs
Jon Heinrichs
Merck Research Laboratories
Boston | United States

Vaccine 2019 May 6;37(20):2679-2686. Epub 2019 Apr 6.

Discovery Drive, Sanofi Pasteur Swiftwater, PA, USA.

After decades of inconsequential infections, and sporadic outbreaks in the Asia-Pacific region between 2007 and 2013, Zika virus caused a widespread epidemic in South America in 2015 that was complicated by severe congenital infections. After the WHO declared a Public Health Emergency of International Concern in February 2016, vaccine development efforts based on different platforms were initiated. Several candidates have since been evaluated in clinical phase I studies. Of these, a Zika purified inactivated vaccine (ZPIV), adjuvanted with aluminum hydroxide, developed by the Walter Reed Army Institute of Research (WRAIR), yielded high seroconversion rates. Sanofi Pasteur further optimized the vaccine in terms of production scale, purification conditions and regulatory compliance, using its experience in flavivirus vaccine development. Here we report that the resulting optimized vaccine (ZPIV-SP) elicited robust seroneutralizing antibody responses and provided complete protection from homologous Zika virus strain challenge in immunocompetent BALB/c mice. ZPIV-SP also showed improved immunogenicity compared with the first-generation vaccine, and improved efficacy in the more permissive interferon receptor-deficient A129 mice. Finally, analysis of the IgG response directed towards nonstructural protein 1 (NS1) suggests that viral NS1 was efficiently removed during the optimized purification process of ZPIV-SP. Together, these results suggest that the optimized vaccine is well suited for further evaluation in larger animal models and late-stage clinical studies.

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Source
http://dx.doi.org/10.1016/j.vaccine.2019.04.013DOI Listing
May 2019

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