Immunogenicity and protection conferred by an optimized purified inactivated Zika vaccine in mice
| Autor: | Sébastien Carayol, Eric Richier, Jon Heinrichs, Marie-Clotilde Bernard, Florence Boudet, Valerie Lecouturier, Catherine C. Berry |
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| Rok vydání: | 2019 |
| Předmět: |
030231 tropical medicine
Enzyme-Linked Immunosorbent Assay Antibodies Viral Zika virus 03 medical and health sciences Mice 0302 clinical medicine Immunogenicity Vaccine Viral Envelope Proteins Interferon Medicine Animals 030212 general & internal medicine Seroconversion Vaccine Potency Mice Knockout General Veterinary General Immunology and Microbiology biology business.industry Zika Virus Infection Immunogenicity Public Health Environmental and Occupational Health Outbreak Viral Vaccines Zika Virus biology.organism_classification Virology Antibodies Neutralizing Flavivirus Disease Models Animal Infectious Diseases Antibody response Vaccines Inactivated Immunoglobulin G Inactivated vaccine Molecular Medicine business medicine.drug |
| Zdroj: | Vaccine. 37(20) |
| ISSN: | 1873-2518 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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