Glycosylation of HIV Env Impacts IgG Subtype Responses to Vaccination

Hess R, Bonsmann MSG, Lapuente D, Maaske A, Kirschning C, Ruland J, Lepenies B, Hannaman D, Tenbusch M, Überla K (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Viruses MDPI

Book Volume: 11

Journal Issue: 2

DOI: 10.3390/v11020153

Abstract

The envelope protein (Env) is the only surface protein of the human immunodeficiency virus (HIV) and as such the exclusive target for protective antibody responses. Experimental evidences from mouse models suggest a modulating property of Env to steer antibody class switching towards the less effective antibody subclass IgG1 accompanied with strong TH2 helper responses. By simple physical linkage we were able to imprint this bias, exemplified by a low IgG2a/IgG1 ratio of antigen-specific antibodies, onto an unrelated antigen, namely the HIV capsid protein p24. Here, our results indicate the glycan moiety of Env as the responsible immune modulating activity. Firstly, in Card9(-/-) mice lacking specific C-Type lectin responsiveness, DNA immunization significantly increased the IgG2a/IgG1 ratio for the Env-specific antibodies while the antibody response against the F-protein of the respiratory syncytial virus (RSV) serving as control antigen remained unchanged. Secondly, sequential shortening of the Env encoding sequence revealed the C2V3 domain as responsible for the strong IgG1 responses and TH2 cytokine production. Removing all potential N-glycosylation sites from the C2V3 domain by site-specific mutagenesis reversed the vaccine-induced immune response towards a Th1-dominated T-cell response and a balanced IgG2a/IgG1 ratio. Accordingly, the stretch of oligomannose glycans in the C2V3 domain of Env might mediate a specific uptake and/or signaling modus in antigen presenting cells by involving interaction with an as yet unknown C-type lectin receptor. Our results contribute to a deeper understanding of the impact of Env glycosylation on HIV antigen-specific immune responses, which will further support HIV vaccine development.

Authors with CRIS profile

Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren Klaus Überla Institute of Clinical and Molecular Virology

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Stiftung Tierärztliche Hochschule Hannover (TiHo) DE Germany (DE) Ichor Medical Systems, Inc. US United States (USA) (US)

How to cite

APA:

Hess, R., Bonsmann, M.S.G., Lapuente, D., Maaske, A., Kirschning, C., Ruland, J.,... Überla, K. (2019). Glycosylation of HIV Env Impacts IgG Subtype Responses to Vaccination. Viruses, 11(2). https://dx.doi.org/10.3390/v11020153

MLA:

Hess, Rebecca, et al. "Glycosylation of HIV Env Impacts IgG Subtype Responses to Vaccination." Viruses 11.2 (2019).

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