title: HIV-1 antibodies and vaccine antigen selectively interact with lipid domains.
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.
authors.affiliation: Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, United States.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hardy
authors.affiliation: Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, United States.
authors.forename: Gene C
authors.initials: GC
authors.lastname: Wong
authors.affiliation: Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, United States.
authors.forename: Rahul
authors.initials: R
authors.lastname: Nayak
authors.affiliation: Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27708, United States.
authors.forename: Kara
authors.initials: K
authors.lastname: Anasti
authors.affiliation: Institute of Nanotechnology (INT) & Karlsruhe Nano Micro Facility (KNMF), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen 76344, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hirtz
authors.affiliation: School of Chemical and Physical Sciences, Flinders University, Bedford Park, South Australia 5042, Australia.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Shapter
authors.affiliation: Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27708, United States.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, United States. Electronic address: zauscher@duke.edu.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zauscher
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry / Q000276:immunology; D017951:Antigen Presentation / Q000187:drug effects*; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice
chemical_list: D016915:AIDS Vaccines; D058846:Antibodies, Monoclonal, Murine-Derived; D015483:HIV Antibodies; D008081:Liposomes
keywords: Atomic force microscopy; Human immunodeficiency virus-1 (HIV-1); Lipid domain; Neutralizing antibody; Supported lipid bilayer