Development of a modular virus-like particle vaccine platform
Abstract/Contents
- Abstract
- Well-designed prophylaxis is always preferable to therapeutic treatment of a disease, and vaccines are second only to sanitation and clean drinking water in promoting global health. Despite their success, current vaccination strategies do not provide broad access to vaccines in the developing world largely due to the expense and cold-chain requirements. Finally, current development and production methods are poorly equipped to respond rapidly to emerging or altered pathogens. This thesis describes the use of the Swartz Lab engineered Hepatitis B core (HepBc) virus-like particle (VLP), a protein-based nanoparticle, as a vaccine platform which overcomes the concerns with current vaccines. Because of the T4 icosahedral assembly of the HepBc dimers, the engineered HepBc VLP scaffold provides 120 sites for the multivalent display of the relevant antigen in a manner that mimics presentation on the natural virus. Here we discuss the development of three antigens to be used in different vaccine candidates based on the HepBc VLP. The first antigen is derived from the Zika virus Protein E, Domain III. This antigen is difficult to produce using traditional protein production methods, but the flexibility of cell-free protein synthesis allows it to be produced with high yields and appropriate folding. The second antigen is derived from the Influenza virus Hemagglutinin Stem and has proven to require extensive protein engineering expertise to stabilize both the correct monomeric and trimeric conformations to provide broadly neutralizing protection against most strains of influenza. Finally, we have worked to produce an antigen derived from the gp41 protein of HIV. This antigen was originally developed in the Kim Lab at Merck Research Labs and had only been produced using peptide synthesis which is not practical for worldwide distribution. Ultimately, these antigens, together with the HepBc VLP scaffold will serve as novel vaccine candidates for Zika, Influenza, and HIV respectively.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Fogarty, Julie Anne |
|---|---|
| Degree supervisor | Swartz, James R |
| Thesis advisor | Swartz, James R |
| Thesis advisor | Dunn, Alexander Robert |
| Thesis advisor | Grimes, Kevin |
| Thesis advisor | Kim, Peter, 1958- |
| Degree committee member | Dunn, Alexander Robert |
| Degree committee member | Grimes, Kevin |
| Degree committee member | Kim, Peter, 1958- |
| Associated with | Stanford University, Department of Chemical Engineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Julie Anne Fogarty. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Julie Anne Fogarty
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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