Antibody Response to Polyhistidine-Tagged Peptide and Protein Antigens Attached to Liposomes via Lipid-Linked Nitrilotriacetic Acid in Mice

Watson, Douglas S.; Platt, Virginia M.; Cao, Limin; Venditto, Vincent J.; Szoka, Francis C.

doi:10.1128/cvi.00425-10

Cited by 56 publications

(60 citation statements)

References 48 publications

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“…The Szoka laboratory previously reported MPER-derived lipopeptides that are potently immunogenic when presented in lipid bilayer vesicles (50,51). In the present study, we generated a series of MPER lipopeptide immunogens bearing anionic side chain modifications that could mimic hydrophilic phospholipid head groups or inflammation-associated PTMs.…”

mentioning

confidence: 99%

Rational Design of Membrane Proximal External Region Lipopeptides Containing Chemical Modifications for HIV-1 Vaccination

Venditto

Watson

Motion

et al. 2013

Clin Vaccine Immunol

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The inability to generate broadly neutralizing antibody (bnAb) responses to the membrane proximal external region (MPER) of HIV-1 gp41 using current vaccine strategies has hampered efforts to prevent the spread of HIV. To address this challenge, we investigated a novel hypothesis to help improve the anti-MPER antibody response. Guided by structural insights and the unique lipid reactivity of anti-MPER bnAbs, we considered whether amino acid side chain modifications that emulate hydrophilic phospholipid head groups could contribute to the generation of 2F5-like or 4E10-like neutralizing anti-MPER antibodies. To test this hypothesis, we generated a series of chemically modified MPER immunogens through derivatization of amino acid side chains with phosphate or nitrate groups. We evaluated the binding affinity of the chemically modified peptides to their cognate monoclonal antibodies, 2F5 and 4E10, using surface plasmon resonance. The modifications had little effect on binding to the antibodies and did not influence epitope secondary structure when presented in liposomes. We selected five of the chemically modified sequences to immunize rabbits and found that an immunogen containing both the 2F5 and 4E10 epitopes and a phosphorylated threonine at T676 elicited the highest anti-peptide IgG titers, although the high antipeptide titers did not confer higher neutralizing activity. These data indicate that side chain modifications adjacent to known neutralizing antibody epitopes are capable of eliciting antibody responses to the MPER but that these chemically modified gp41 epitopes do not induce neutralizing antibodies.

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confidence: 99%

Rational Design of Membrane Proximal External Region Lipopeptides Containing Chemical Modifications for HIV-1 Vaccination

Venditto

Watson

Motion

et al. 2013

Clin Vaccine Immunol

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“…Nickel-chelating liposomes have also been prepared by incorporating nitrilotriacetic acid lipid derivatives into the liposomes to promote bonding to polyhistidinylated OVA antigens [28]. The liposomes were composed of DOGS-NTANi, dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG), cholesterol, and MPL.…”

Section: Liposomesmentioning

confidence: 99%

Nanotechnology and vaccine development

Kim

Park

Shon

et al. 2014

Asian Journal of Pharmaceutical Sciences

119

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Emulsions Polymeric nanocarriersCarbon nanomaterials a b s t r a c t Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development.Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrierbased vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

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“…It was shown that Ni-NTA3-DTDA liposomes (containing three functional chelating lipid) with single-chain Fv fragments (anti CD11c) bound onto the liposomal surface were able to target dendritic cells in vitro as well as in vivo. The application of Ni-NTA3-DTDA probably endows the metallochelating bond with a higher in vivo stability [ 63 ], but this improved stability did not infl uence higher immunogenicity [ 64 ]. Generally, metal ions, physicochemical character of the metallochelating lipids, and their surface density belong to the factors that could be optimised to get a required in vivo stability and therefore strong immune response.…”

Section: Metallochelating Bond and Metallochelating Liposomesmentioning

confidence: 99%

Functionalised Nanoliposomes for Construction of Recombinant Vaccines: Lyme Disease as an Example

et al. 2013

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Liposomes (phospholipid bilayer vesicles) represent an almost ideal carrier system for the preparation of synthetic vaccines due to their biodegradability and capacity to protect and transport molecules of different physicochemical properties (including size, hydrophilicity, hydrophobicity, and charge). Liposomal carriers can be applied by invasive (e.g. i.m ., s.c ., i.d .) as well as non-invasive (transdermal and mucosal) routes. In the last 15 years, liposome vaccine technology has matured and several vaccines containing liposome-based adjuvants have been approved for human and veterinary use or have reached late stages of clinical evaluation.Given the intensifying interest in liposomebased vaccines, it is important to understand precisely how liposomes interact with the immune system and how they stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines -method of antigen attachment, lipid composition, bilayer fl uidity, particle charge, and other properties -exert strong effects on the resulting immune response. In this chapter

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Antibody Response to Polyhistidine-Tagged Peptide and Protein Antigens Attached to Liposomes via Lipid-Linked Nitrilotriacetic Acid in Mice

Cited by 56 publications

References 48 publications

Rational Design of Membrane Proximal External Region Lipopeptides Containing Chemical Modifications for HIV-1 Vaccination

Rational Design of Membrane Proximal External Region Lipopeptides Containing Chemical Modifications for HIV-1 Vaccination

Nanotechnology and vaccine development

Functionalised Nanoliposomes for Construction of Recombinant Vaccines: Lyme Disease as an Example

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