Plant-produced, trans-encapsidated, replicative viral nanoparticles as a vaccine platform.

Zhou, Yiyang, 1988-

Plant-produced, trans-encapsidated, replicative viral nanoparticles as a vaccine platform.

dc.contributor.advisor	Kearney, Christopher Michel, 1958-
dc.creator	Zhou, Yiyang, 1988-
dc.date.accessioned	2016-09-01T13:03:57Z
dc.date.available	2016-09-01T13:03:57Z
dc.date.created	2016-08
dc.date.issued	2016-08-01
dc.date.submitted	August 2016
dc.date.updated	2016-09-01T13:03:57Z
dc.description.abstract	Replicative virus-based vaccines provide potential solutions to avoid the natural deficits of traditional single-protein subunit vaccines. Unlike subunit vaccines, the infectious nature of viral particles can stimulate the innate immune response, which allows enhanced and elongated stimulation of antibody and T cell adaptive immunity. When these replicative vaccines are engineered to express antigen genes naturally in the patient's cells, cell mediated immunity is stimulated via the class I antigen presentation pathway, followed by a robust CD8+ T cell activation and interferon production. In this study, I aim to develop a safe, effective and cost-efficient transencapsidated replicative vaccine platform by encapsidating within strongly immunogenic tobacco mosaic virus (TMV) nanoparticles the self-replicative RNA of Flock House virus (FHV), an insect virus that also replicates in human and plant cells. By inserting the unique packaging signal of TMV into FHV RNA, the capsid of TMV assembles around the heterologous RNA, when TMV coat protein and FHV RNA are expressed in the same cell. First, the replication of different viral delivery vectors in both mammalian cells and plant cells was investigated and their cellular co-infection was demonstrated. The resulting successfully packaged chimeric nanoparticle improved antibody production over the standards after vaccination in mice. Next I detailed the specifics and techniques required to produce and purify these nanoparticle vaccines in planta via agroinoculation. To further explore the possibility of increasing the yield of plant-produced nanoparticle vaccines, an optimized spray-on inoculation method was developed using a low-toxicity surfactant to aid agro-inoculation. Unexpectedly, this also decreased contaminating plant pathogenesis-related proteins. A continuing study is also discussed on trans-locating FHV replication to endoplasmic reticulum, which suggests potential to further increase plant yield of nanoparticle vaccines as well.
dc.format.mimetype	application/pdf
dc.identifier.uri	http://hdl.handle.net/2104/9799
dc.language.iso	en
dc.rights.accessrights	Worldwide access.
dc.rights.accessrights	Access changed 1/7/2019.
dc.subject	Virus. Vaccine.
dc.title	Plant-produced, trans-encapsidated, replicative viral nanoparticles as a vaccine platform.
dc.type	Thesis
dc.type.material	text
local.embargo.lift	2018-08-01
local.embargo.terms	2018-08-01
thesis.degree.department	Baylor University. Institute of Biomedical Studies.
thesis.degree.grantor	Baylor University
thesis.degree.level	Doctoral
thesis.degree.name	Ph.D.