UNIGE document Scientific Article
previous document  unige:80122  next document
add to browser collection
Title

Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

Authors
Malinge, Pauline
Magistrelli, Giovanni
show hidden authors show all authors [1 - 18]
Published in PLOS Pathogens. 2015, vol. 11, no. 11, p. e1005276
Abstract Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein's globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy.
Identifiers
PMID: 26587982
Full text
Article (Published version) (3.5 MB) - public document Free access
Structures
Research group Centre de Vaccinologie et d'Immunologie néonatale (177)
Citation
(ISO format)
SOMMERSTEIN, Rami et al. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection. In: PLOS Pathogens, 2015, vol. 11, n° 11, p. e1005276. https://archive-ouverte.unige.ch/unige:80122

169 hits

43 downloads

Update

Deposited on : 2016-01-29

Export document
Format :
Citation style :