Tran, My Kim ORCID: 0009-0000-3449-6719 (2024). Identification of a novel broadly neutralizing antibody targeting HIV-1. PhD thesis, Universität zu Köln.
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Identification of a broadly neutralizing antibody targeting HIV-1.pdf - Accepted Version Download (3MB) |
Abstract
Despite 40 years of research and more than 25 years of effective antiretroviral therapy (ART), HIV-1 infection remains a tremendous public health problem in both developing and industrialized countries. With a recent incidence of 1.5 million the UNAIDS goals of 500,000 new infections calculated in 2016 were dramatically missed. Therefore, new approaches to combat HIV-1 pandemic are needed. HIV-1 research regarding ‘Broadly neutralizing antibodies’ has paved the way for developing effectively used antibody therapies against SARS-CoV-2 and Ebola virus, showing that antibody therapies can be effectively used against infectious diseases. In general, bNAbs against HIV-1 were demonstrated to be safe and effective in infected individuals, but finally lead to viral escape because of the high mutation rate of HIV-1. Combi-therapies were implemented to address this problem and could prolong viral suppression compared to monotherapy. Still, for effective long-lasting viral suppression new potent bNAbs are needed to finally restrict viral escape. To this end, we characterized the HIV-1 specific B cell repertoire of an individual with potent serum neutralization of HIV-1, a so-called Elite Neutralizer, as this approach was previously successful for the isolation of existing bNAbs. The serum neutralization of Elite Neutralizer IDC561 ranked among the top 1% of a cohort of 2,274 HIV-1 infected individuals. From IDC561’s HIV-1 reactive B cell clones we amplified single cell sequences, allowing for antibody cloning and production. Testing isolated antibodies for their binding capacities and neutralizing activity lead to the isolation of 1-18, a broad and neutralizing antibody, which showed exceptional neutralizing activity. 1-18 exceeded neutralization activity in comparison to clinically advanced bNAbs not only in the 12-strain global panel but also in 119-pseudovirus multiclade and 100-pseudovirus clade C panels, which makes 1-18 a promising option for HIV 1 antibody therapy.
Item Type: | Thesis (PhD thesis) | ||||||||||
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URN: | urn:nbn:de:hbz:38-736479 | ||||||||||
Date: | 2024 | ||||||||||
Place of Publication: | Köln | ||||||||||
Language: | English | ||||||||||
Faculty: | Faculty of Medicine | ||||||||||
Divisions: | Faculty of Medicine > Virologie > Institut für Virologie | ||||||||||
Subjects: | Natural sciences and mathematics Life sciences Medical sciences Medicine |
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Date of oral exam: | 11 July 2024 | ||||||||||
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Refereed: | Yes | ||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/73647 |
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