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9/26/2014  |   10:45 AM - 11:15 AM   |  Topical Session 2   |  Ballroom A

A prophylactic HCMV vaccine to prevent congenital infection using enveloped virus-like-particles (eVLPs) induces potent immunity greater than natural infection

A prophylactic vaccine to prevent congenital transmission of human Cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in immunosuppressed recipients of HCMV-infected solid organ transplants would be highly desirable. Neutralizing antibodies against HCMV confer significant protection, and gB is a major target of such neutralizing antibodies. However, one shortcoming of past HCMV vaccines may have been a failure to induce high titer persistent neutralizing antibody responses that could prevent infection of epithelial cells. We have used enveloped virus-like-particles (eVLPs), in which particles were produced in cells after expression of murine leukemia virus (MLV) viral matrix protein Gag, to express the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV) G protein (gB-G eVLPs). gB-G expressing eVLPs induce potent neutralizing antibodies in mice with a much greater propensity for epithelial cell neutralizing activity than that induced with soluble recombinant gB protein. Analysis of gB antibody binding titers and T helper cell responses demonstrated that high neutralizing antibody titers were not associated with enhanced immunogenicity of the gB-G eVLPs, rather, with an optimal gB conformation like that of infected cells and viral particles. gB-G eVLPs have been produced in GMP-compliant HEK 293 cells and purified to meet or exceed criteria established by the FDA for licensed human vaccines. After absorbing gB-G eVLPs to alum, the potency of our clinical candidate exceeds levels of naturally acquired immunity, and represents a novel, safe approach to an efficacious prophylactic CMV vaccine.

David E Anderson (Primary Presenter), danderson@vbivaccines.com;
Dr. Anderson is a co-founder of VBI Vaccines, a vaccine development company dedicated to innovative formulation, development & delivery of vaccines that expand coverage and enhance protection in both established and emerging markets. He currently serves as Vice President, Research, and is actively involved in management of preclinical research efforts and for building and protecting VBI’s intellectual property. Prior to joining VBI, Dr. Anderson directed academic research as an Assistant Professor at Harvard Medical School. At Harvard he developed a multi-disciplinary research program focused on elucidating mechanisms by which inflammation is regulated, with general relevance to the fields of autoimmunity and tumor immunotherapy. He is a highly published investigator, appearing as primary author on studies appearing in the most prestigious scientific journals, including Nature and Science. He has been invited to give lectures at international conferences in the United States and abroad.

ASHA DISCLOSURE:

Financial - Receives Salary,Ownership interest for Employment,Management position,Ownership from VBI Vaccines.  

Nonfinancial - No relevant nonfinancial relationship exist.

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