Universität zu Köln

Meijers, Matthijs ORCID: 0000-0002-1876-8064, Vanshylla, Kanika ORCID: 0000-0003-4552-9170, Gruell, Henning, Klein, Florian and Laessig, Michael (2021). Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody. Proc. Natl. Acad. Sci. U. S. A., 118 (30). WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Broadly neutralizing antibodies are promising candidates for treatment and prevention of HIV-1 infections. Such antibodies can temporarily suppress viral load in infected individuals; however, the virus often rebounds by escape mutants that have evolved resistance. In this paper, we map a fitness model of HIV-1 interacting with broadly neutralizing antibodies using in vivo data from a recent clinical trial. We identify two fitness factors, antibody dosage and viral load, that determine viral reproduction rates reproducibly across different hosts. The model successfully predicts the escape dynamics of HIV-1 in the course of an antibody treatment, including a characteristic frequency turnover between sensitive and resistant strains. This turnover is governed by a dosage-dependent fitness ranking, resulting from an evolutionary trade-off between antibody resistance and its collateral cost in drug-free growth. Our analysis suggests resistance-cost tradeoff curves as a measure of antibody performance in the presence of resistance evolution.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Meijers, Matthijs UNSPECIFIED orcid.org/0000-0002-1876-8064 UNSPECIFIED Vanshylla, Kanika UNSPECIFIED orcid.org/0000-0003-4552-9170 UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Laessig, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-574837
DOI:	10.1073/pnas.2104651118
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	118
Number:	30
Date:	2021
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FITNESS; EVOLUTION; RESISTANCE; SELECTION; THERAPY; VIREMIA; PROTEIN; VRC01; MODEL; COST Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57483