Protection against lethal challenge by Ebola virus-like particles produced in insect cells

• Authors: Yuliang Sun, Emory University; Ricardo Carrion, Southwest Foundation for Biomedical Research; Ling Ye, Emory University; Zhiyuan Wen, Emory University; Young-Tae Ro, Konkuk University; Kathleen Brasky, Southwest Foundation for Biomedical Research; Anysha E. Ticer, Southwest Foundation for Biomedical Research; E. Ellen Schwegler, Southwest Foundation for Biomedical Research; Jean L. Patterson, Southwest Foundation for Biomedical Research; Richard W Compans, Emory University; Chinglai Yang, Emory University
• Journal Title: Virology
• Volume: Volume 383, Number 1
• Publisher: Elsevier | 2009-01-05, Pages 12-21
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.virol.2008.09.020
• Subjects: Biology, Virology; Health Sciences, Immunology
• Keywords: Ebola virus; Virus like particle; Antibody; Lethal challenge; Vaccine

Abstract

Ebola virus-like particles (VLPs) were produced in insect cells using a recombinant baculovirus expression system and their efficacy for protection against Ebola virus infection was investigated. Two immunizations with 50 ug Ebola VLPs (high dose) induced a high level of antibodies against Ebola GP that exhibited strong neutralizing activity against GP-mediated virus infection and conferred complete protection of vaccinated mice against lethal challenge by a high dose of mouse-adapted Ebola virus. In contrast, two immunizations with 10 ug Ebola VLPs (low dose) induced 5-fold lower levels of antibodies against GP and these mice were not protected against lethal Ebola virus challenge, similar to control mice that were immunized with 50 ug SIV Gag VLPs. However, the antibody response against GP were boosted significantly after a third immunization with 10 ug Ebola VLPs to similar levels as those induced by two immunizations with 50 ug Ebola VLPs, and vaccinated mice were also effectively protected against lethal Ebola virus challenge. Furthermore, serum viremia levels in protected mice were either below the level of detection or significantly lower compared to the viremia levels in control mice. These results show that effective protection can be achieved by immunization with Ebola VLPs produced in insect cells, which give high production yields, and lend further support to their development as an effective vaccine strategy against Ebola virus.