| Single-dose immunization with virus replicon particles confers rapid robust protection against Rift Valley fever virus challenge. | |
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MedLine Citation:
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PMID: 22345465 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The potential for RVFV introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. Here, we demonstrate a robust system for the reverse genetics generation of a RVF virus replicon particle (VRP(RVF)) vaccine candidate. Using a mouse model, we show that VRP(RVF) immunization provides the optimal balance of safety and single-dose robust efficacy. VRP(RVF) can actively synthesize viral RNA and proteins but lacks structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. VRP(RVF) proved to be completely safe following intracranial inoculation of suckling mice, a stringent test of vaccine safety. Single-dose subcutaneous immunization with VRP(RVF), although it is highly attenuated, completely protected mice against a virulent RVFV challenge dose which was 100,000-fold greater than the 50% lethal dose (LD(50)). Robust protection from lethal challenge was observed by 24 h postvaccination, with 100% protection induced in as little as 96 h. We show that a single subcutaneous VRP(RVF) immunization initiated a systemic antiviral state followed by an enhanced adaptive response. These data contrast sharply with the much-reduced survivability and immune responses observed among animals immunized with nonreplicating viral particles, indicating that replication, even if confined to the initially infected cells, contributes substantially to protective efficacy at early and late time points postimmunization. These data demonstrate that replicon vaccines successfully bridge the gap between safety and efficacy and provide insights into the kinetics of antiviral protection from RVFV infection. |
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Authors:
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Kimberly A Dodd; Brian H Bird; Maureen G Metcalfe; Stuart T Nichol; César G Albariño |
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Publication Detail:
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Type: Journal Article Date: 2012-02-15 |
Journal Detail:
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Title: Journal of virology Volume: 86 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-29 Completed Date: 2012-06-18 Revised Date: 2013-02-08 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 4204-12 Citation Subset: IM |
Affiliation:
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Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Neutralizing / immunology Antibodies, Viral / immunology Cell Line Female Gene Expression Gene Expression Regulation / immunology Gene Order Immunoglobulin G / immunology Mice Mice, Inbred C57BL Rift Valley Fever / genetics, immunology*, mortality Rift Valley fever virus / growth & development, immunology*, ultrastructure Survival Analysis Viral Vaccines / administration & dosage, immunology* Virion / growth & development, immunology*, ultrastructure Virus Replication / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neutralizing; 0/Antibodies, Viral; 0/Immunoglobulin G; 0/Viral Vaccines |
| Comments/Corrections | |
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