Probing the groove epitope on HIV-1 GP41 for sensitivity to neutralizing antibodies
Abstract/Contents
- Abstract
- The Human Immunodeficiency Virus (HIV) has been a public health scourge since its appearance in the early 1980s. Having spread its way from sub-Saharan Africa across the world, now 1 in 200 people living on earth is infected with the virus. Because there is currently no cure, everyone infected with HIV will progress to Acquired Immunodeficiency Syndrome (AIDs), where they will succumb to an AIDs-related illness. Our growing understanding of the molecular mechanisms of the HIV virus has greatly aided the development of new therapeutics. HIV is a membrane virus containing only one viral protein on its surface, the envelope glycoprotein (Env). Env is responsible for mediating the fusion of the viral membrane with the membrane of the target cell. Antibodies towards Env block membrane fusion and prevent infection. Because HIV mutates rapidly resulting in a diverse array of clinical isolates, strategies aimed at eliciting neutralizing antibodies have failed. This is due to these antibodies being strain-specific and unable to provide protection against the many clinical isolates. The recent discovery of broadly neutralizing antibodies has re-invigorated the search for a vaccine. These antibodies target conserved regions on Env and thus are able to provide protection against a diverse range of clinical isolates. This dissertation focuses on our findings characterizing the most conserved region of Env, the groove region of the gp41 N-heptad repeat. We first design and validate new mimetics of the N-heptad repeat. Second, we use these mimetics to select for monoclonal antibodies. Third, we immunize guinea pigs to test whether these mimetics are capable of eliciting neutralizing antibodies. Finally, we investigate strategies for improving the potency of N-heptad repeat antibodies through the use of drug combinations. Together, these finding suggest that antibodies towards the groove epitope, though weakly neutralizing, may be a viable vaccine strategy.
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 | Brown, Clayton Laroy |
|---|---|
| Degree supervisor | Kim, Peter, 1958- |
| Thesis advisor | Kim, Peter, 1958- |
| Thesis advisor | Harbury, Pehr |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Pfeffer, Suzanne |
| Degree committee member | Harbury, Pehr |
| Degree committee member | Khosla, Chaitan, 1964- |
| Degree committee member | Pfeffer, Suzanne |
| Associated with | Stanford University, Department of Biochemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Clayton L. Brown Jr. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Clayton Laroy Brown
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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