Developing VHH-based tools to study Ebolavirus infection

Variable domains of camelid-derived heavy chain-only antibodies, or VHHs, have emerged as a unique antigen binding moiety that holds promise in its versatility and utilization as a tool to study biological questions. This thesis focuses on two aspects on developing tools to study infectious disease, specifically Ebolavirus entry. In Chapter 1, I provide an overview about antibodies and how antibodies have transformed the biomedical field and how single domain antibody fragments, or VHHs, have entered this arena. I will also touch upon how VHHs have been used in various fields and certain aspects that remain underexplored. Chapter 2 focuses on the utilization of VHHs to study Ebolavirus entry using VHHs that were isolated from alpacas. Two VHHs were found to neutralize Ebolavirus in both Biosafety Level 2 and 4 laboratory conditions. Ongoing experiments to address mechanism focuses on two aspects of neutralization: Cathepsin inhibition or NPC1-mediated inhibition. Finally, Chapter 3 discusses the overall landscape for Ebolavirus therapeutics and will discuss future directions of this work.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Nguyen, Jason V. M. H.(Jason Vu Minh Hien)

Advisor dc:contributor.advisor

• Hidde L. Ploegh.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/122421

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/122421