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

Publication ,  Journal Article
Hardy, GJ; Wong, GC; Nayak, R; Anasti, K; Hirtz, M; Shapter, JG; Alam, SM; Zauscher, S
Published in: Biochim Biophys Acta
October 2014

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.

Duke Scholars

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

October 2014

Volume

1838

Issue

10

Start / End Page

2662 / 2669

Location

Netherlands

Related Subject Headings

  • Mice
  • Membrane Microdomains
  • Liposomes
  • Humans
  • HIV-1
  • HIV Antibodies
  • Cell Line
  • Biomimetic Materials
  • Antigen Presentation
  • Antibodies, Monoclonal, Murine-Derived
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hardy, G. J., Wong, G. C., Nayak, R., Anasti, K., Hirtz, M., Shapter, J. G., … Zauscher, S. (2014). HIV-1 antibodies and vaccine antigen selectively interact with lipid domains. Biochim Biophys Acta, 1838(10), 2662–2669. https://doi.org/10.1016/j.bbamem.2014.07.007
Hardy, Gregory J., Gene C. Wong, Rahul Nayak, Kara Anasti, Michael Hirtz, Joseph G. Shapter, S Munir Alam, and Stefan Zauscher. “HIV-1 antibodies and vaccine antigen selectively interact with lipid domains.Biochim Biophys Acta 1838, no. 10 (October 2014): 2662–69. https://doi.org/10.1016/j.bbamem.2014.07.007.
Hardy GJ, Wong GC, Nayak R, Anasti K, Hirtz M, Shapter JG, et al. HIV-1 antibodies and vaccine antigen selectively interact with lipid domains. Biochim Biophys Acta. 2014 Oct;1838(10):2662–9.
Hardy, Gregory J., et al. “HIV-1 antibodies and vaccine antigen selectively interact with lipid domains.Biochim Biophys Acta, vol. 1838, no. 10, Oct. 2014, pp. 2662–69. Pubmed, doi:10.1016/j.bbamem.2014.07.007.
Hardy GJ, Wong GC, Nayak R, Anasti K, Hirtz M, Shapter JG, Alam SM, Zauscher S. HIV-1 antibodies and vaccine antigen selectively interact with lipid domains. Biochim Biophys Acta. 2014 Oct;1838(10):2662–2669.

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

October 2014

Volume

1838

Issue

10

Start / End Page

2662 / 2669

Location

Netherlands

Related Subject Headings

  • Mice
  • Membrane Microdomains
  • Liposomes
  • Humans
  • HIV-1
  • HIV Antibodies
  • Cell Line
  • Biomimetic Materials
  • Antigen Presentation
  • Antibodies, Monoclonal, Murine-Derived