HIV-1 antibodies and vaccine antigen selectively interact with lipid domains

Gregory Hardy, Gene Wong, Rahul Nayak, Kara Anasti, Michael Hirtz, Joseph Shapter, S Munir Alam, Stefan Zauscher

    Research output: Contribution to journalArticlepeer-review

    3 Citations (Scopus)

    Abstract

    The rare, broadly neutralizing antibodies, 4E10 and 2F5, that target the HIV-1 membrane proximal external region also associate with HIV-1 membrane lipids as part of a required first-step in HIV-1 neutralization. HIV-1 virions have high concentration of cholesterol and sphingomyelin, which are able to organize into liquid-ordered domains (i.e., lipid rafts), and could influence the interaction of neutralizing antibodies with epitopes proximal to the membrane. The objective of this research is to understand how these lipid domains contribute to 2F5/4E10 membrane interactions and to antigen presentation in liposomal form of HIV-1 vaccines. To this end we have engineered biomimetic supported lipid bilayers and are able to use atomic force microscopy to visualize membrane domains, antigen clustering, and antibody-membrane interactions. Our results demonstrate that 2F5/4E10 do not interact with highly ordered gel and liquid-ordered domains and exclusively bind to a liquid-disordered lipid phase. This suggests that vaccine liposomes that contain key viral membrane components, such as high cholesterol content, may not be advantageous for 2F5/4E10 vaccine strategies. Rather, vaccine liposomes that primarily contain a liquid-disordered phase may be more likely to elicit production of lipid reactive, 2F5- and 4E10-like antibodies.

    Original languageEnglish
    Pages (from-to)2662-2669
    Number of pages8
    JournalBiochimica Et Biophysica Acta (BBA) - Biomembranes
    Volume1838
    Issue number10
    DOIs
    Publication statusPublished - Oct 2014

    Keywords

    • Atomic force microscopy
    • Human immunodeficiency virus-1 (HIV-1)
    • Lipid domain
    • Neutralizing antibody
    • Supported lipid bilayer

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