Engineering protein antigens to refocus the immune response

Arsiwala, Ammar Mazhar

Title:

Engineering protein antigens to refocus the immune response

dc.contributor.advisor	Kane, Ravi S.
dc.contributor.author	Arsiwala, Ammar Mazhar
dc.contributor.committeeMember	Prausnitz, Mark
dc.contributor.committeeMember	Champion, Julie
dc.contributor.committeeMember	Platt, Manu
dc.contributor.committeeMember	Sulchek, Todd
dc.contributor.department	Chemical and Biomolecular Engineering
dc.date.accessioned	2020-09-08T12:42:31Z
dc.date.available	2020-09-08T12:42:31Z
dc.date.created	2019-08
dc.date.issued	2019-07-24
dc.date.submitted	August 2019
dc.date.updated	2020-09-08T12:42:31Z
dc.description.abstract	Infectious diseases continue to be a threat to millions globally – largely because of highly effective immune evasion mechanisms evolved in pathogens. Our work focuses on engineering proteins to shield selected epitopes thereby refocusing the immune response to other regions on the protein antigen. In the context of vaccine design, nanopatterning can help preferentially elicit broadly neutralizing antibodies while suppressing the response to epitopes that serve as immunological decoys. We have developed two approaches to achieve this shielding and refocusing – one referred to as “Nanopatterning” that uses site-specifically conjugated polymeric shields and a second approach that uses engineered antibody fragments (Fabs) as shielding agents. Using these tools, we have demonstrated the ability to refocus the immune response to broadly neutralizing epitopes of medically relevant antigens from diseases including Malaria, Influenza and Zika. In summary, this work explores two new approaches to achieve immunofocusing – allowing refocusing of the immune response to broadly neutralizing epitopes of protein antigens. These tools should be broadly applicable for the design of broadly protective vaccines against pathogens such as malarial parasites, influenza, flaviviruses and HIV.
dc.description.degree	Ph.D.
dc.format.mimetype	application/pdf
dc.identifier.uri	http://hdl.handle.net/1853/63560
dc.language.iso	en_US
dc.publisher	Georgia Institute of Technology
dc.subject	Immunofocusing
dc.subject	Vaccines
dc.subject	Nanopatterning
dc.subject	Broadly neutralizing antibodies
dc.title	Engineering protein antigens to refocus the immune response
dc.type	Text
dc.type.genre	Dissertation
dspace.entity.type	Publication
local.contributor.advisor	Kane, Ravi S.
local.contributor.corporatename	School of Chemical and Biomolecular Engineering
local.contributor.corporatename	College of Engineering
relation.isAdvisorOfPublication	35bafb8e-f759-4618-9d00-c736c2303f60
relation.isOrgUnitOfPublication	6cfa2dc6-c5bf-4f6b-99a2-57105d8f7a6f
relation.isOrgUnitOfPublication	7c022d60-21d5-497c-b552-95e489a06569
thesis.degree.level	Doctoral