HIV-1 antibodies and vaccine antigen selectively interact with lipid domains.
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Hardy, GJ; Wong, GC; Nayak, R; Anasti, K; Hirtz, M; Shapter, JG; Alam, SM; Zauscher, S
Published Date
- October 2014
Published In
Volume / Issue
- 1838 / 10
Start / End Page
- 2662 - 2669
PubMed ID
- 25019685
Pubmed Central ID
- 25019685
International Standard Serial Number (ISSN)
- 0006-3002
Digital Object Identifier (DOI)
- 10.1016/j.bbamem.2014.07.007
Language
- eng
Conference Location
- Netherlands