Engineering of human papillomavirus l1 virus-like particle to use as a scaffold for vaccines
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Authors
Yuan, Xinmeng
Issue Date
2024-05
Type
Electronic thesis
Thesis
Thesis
Language
en_US
Keywords
Biochemistry and biophysics
Alternative Title
Abstract
Vaccines are powerful therapeutics used to prevent and eradicate deadly infectious diseases, such as smallpox, and to reduce diseases such as polio, measles, tetanus, and more recently, the SARS-CoV-2 virus that caused the COVID-19 pandemic. Vaccines provide active acquired immunity toward a specific infectious disease, where the vaccine closely resembles the antigen, so that the immune system can recognize it as foreign, attacks it, and remembers it. This "remembering" is what makes vaccines so powerful; anything that resembles the antigen will be destroyed by the immune system in the future, providing long-lasting immunity. The first few vaccines developed were inactivated or attenuated viruses. Most of the vaccines in the world are usually in the form of subunit protein and adenovirus vaccines, but more recently, because of the COVID-19 pandemic, the emergency usage of mRNA-based vaccines has been implemented.Vaccine technology can also be applied in a nontraditional fashion, such as a contraceptive vaccine, where the vaccine target is pregnancy instead of a disease, to address the unmet need of a non-hormonal and non-invasive form of contraception. Therefore, we propose to design and engineer the Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) to be used as a scaffold for vaccines by inserting desired antigens. This means that this scaffold can be used for essentially any pathogen. Any peptide-based antigens can be engineered onto the surface of the VLP so that a vaccine against that antigen can be made. We propose to use VLP as a scaffold for a unique contraceptive vaccine, where the purpose of the vaccine is to prevent pregnancy. We also propose to use the VLP as a scaffold for a glycan-free COVID vaccine to minimize the occurrence of autoimmune diseases. Through this process, we have discovered ways to optimally assemble the VLP in our expression and production system. Lastly, we have engineered a small VLP, which is half the size of regular HPV VLP, that can also be utilized as a scaffold for different purposes with the intent of providing shorter immunity in the context of a contraceptive vaccine so that people will have different options for contraceptive duration.
This work focuses on the design of the VLP scaffold to accommodate different epitopes for a unique contraceptive vaccine and a glycan-free COVID vaccine, the methods to optimally produce the vaccines, and the ways to engineer a small-sized VLP to also be used as a scaffold.
Description
May2024
School of Science
School of Science
Full Citation
Publisher
Rensselaer Polytechnic Institute, Troy, NY