Universität zu Köln

LaMont, Colin, Otwinowski, Jakub, Vanshylla, Kanika, Gruell, Henning, Klein, Florian ORCID: 0000-0003-1376-1792 and Nourmohammad, Armita (2022). Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1. eLife, 11. CAMBRIDGE: eLIFE SCIENCES PUBL LTD. ISSN 2050-084X

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Abstract

Infusion of broadly neutralizing antibodies (bNAbs) has shown promise as an alternative to anti-retroviral therapy against HIV. A key challenge is to suppress viral escape, which is more effectively achieved with a combination of bNAbs. Here, we propose a computational approach to predict the efficacy of a bNAb therapy based on the population genetics of HIV escape, which we parametrize using high-throughput HIV sequence data from bNAb-naive patients. By quantifying the mutational target size and the fitness cost of HIV-1 escape from bNAbs, we predict the distribution of rebound times in three clinical trials. We show that a cocktail of three bNAbs is necessary to effectively suppress viral escape, and predict the optimal composition of such bNAb cocktail. Our results offer a rational therapy design for HIV, and show how genetic data can be used to predict treatment outcomes and design new approaches to pathogenic control.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code LaMont, Colin UNSPECIFIED UNSPECIFIED UNSPECIFIED Otwinowski, Jakub UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanshylla, Kanika UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED orcid.org/0000-0003-1376-1792 UNSPECIFIED Nourmohammad, Armita UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-681863
DOI:	10.7554/eLife.76004
Journal or Publication Title:	eLife
Volume:	11
Date:	2022
Publisher:	eLIFE SCIENCES PUBL LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MINIMUM HELLINGER DISTANCE; STRUCTURAL BASIS; VACCINE; DYNAMICS; VIRUS; PROSPECTS; ESCAPE; CONSEQUENCES; CHALLENGES; CLEARANCE Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68186