Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine Development: A Virus-Like Particle Vaccine Approach

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 as a highly infectious virus that spread rapidly and was declared a pandemic by the World Health Organization (WHO) in March of 2020.1 SARS-CoV-2 infection causes respiratory disease (Coronavirus Disease; COVID-19), and during the initial infection wave of the pandemic, disease severity ranged from asymptomatic to mild upper respiratory disease, to severe pneumonia resulting in hospitalization and death.1 To date, over 750 million cases of COVID-19 and almost 7 million deaths due to the disease have been confirmed (WHO COVID-19 Dashboard). Virus-like particles are nanoparticles made up of existing viral structural proteins that will assemble into a particle form. The hepatitis B virus core antigen (∆HBcAg) is a stable VLP that will maintain its ability to fold into a viral particle following incorporation of foreign epitopes into its protein sequence. In this project, we produced a vaccine against SARS-CoV-2 that was composed of three SARS-CoV-2 Spike protein epitopes inserted into the ∆HBcAg VLP. These insertions included Spike epitopes predicted to induce a humoral and/or cell-mediated immune response. The immunogenicity of the resultant vaccine was tested utilizing a K18-hACE2 transgenic C57BL/6 mouse model. Mice were challenged with live SARS-CoV-2 three weeks after the final booster dose and the vaccine was evaluated for protective efficacy. Results of these studies showed epitope-specific humoral and cell-mediated immune responses, but these responses were insufficient in protecting against SARS-CoV-2 infection.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biomedical and Veterinary Sciences

Department dc:contributor.department

Biomedical and Veterinary Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2023

Author dc:creator

• Hassebroek, Anna Marie

Chair dc:contributor.committeechair

• Meng, Xiang-Jin

Committee members dc:contributor.committeemember

• Duggal, Nisha K.
• Yuan, Lijuan
• Zhang, Chenming
• LeRoith, Tanya

• SARS-CoV-2
• Hepatitis B core antigen protein
• Virus-like particle

Statement dc:rights

• Creative Commons Attribution-NonCommercial 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc/4.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:39058

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/117180