Parameters affecting the immunogenicity of a liposome‐associated synthetic hexapeptide antigen

Frisch, Benoı̂t; Muller, Sylviane; Briand, Jean Paul; Regenmortel, M.H.V. Van; Schuber, Francis

doi:10.1002/eji.1830210128

Cited by 45 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the size and complexity of the antigen decreases, the benefit of surface conjugation for antibody induction becomes more pronounced. Synthetic peptides for which surface conjugation provides superior immune responses to encapsulation include those derived from viral antigens (HIV-1 gp120, HSV glycoprotein D) and tumor antigens (MUC1) [70, 74–77]. …”

Section: Physicochemical Properties Of Liposomal Vaccines Evaluatementioning

confidence: 99%

Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

Watson

Endsley

Huang

2012

Vaccine

278

193

View full text Add to dashboard Cite

Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines – method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties – exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study.

show abstract

Section: Physicochemical Properties Of Liposomal Vaccines Evaluatementioning

confidence: 99%

Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

Watson

Endsley

Huang

2012

Vaccine

278

193

View full text Add to dashboard Cite

show abstract

“…must contain an adjuvant such as monophosphoryl lipid A (MPL) (20,21). This latter amphipathic molecule, which is a non-toxic derivative of the lipopolysaccharide, is a macrophage activator and a B-lymphocyte mitogen that is currently tested in humans (22).…”

Section: Stealth@ Liposomes and (Targeted) Drug Deliverymentioning

confidence: 99%

Liposomes: from membrane models to gene therapy

Schuber¹,

Kichler²,

Boeckler³

et al. 1998

Pure and Applied Chemistry

Self Cite

View full text Add to dashboard Cite

Liposomes, which are self-closed vesicular structures composed of (phospho)lipid bilayers, have attracted considerable interest since their discovery in the 60's. Because of their organization and the versatility of their physicochemical properties these vesicles have been extensively studied as models for biological membranes. Since liposomes can sequester bioactive molecules, they are also widely used as drug delivej systems. The present report focuses on the renewed interest in the field with the advent of "sterically stabilized" (Stealth@) liposomes which, compared to "conventional" liposomes, have much longer circulation times in vivo, and on the use of cationic liposomes in non-viral gene delivery strategies. Liposomes are also very promising antigen carriers that can be used to design peptide-based synthetic vaccines.

show abstract

“…Results reported in this paper show that MAP 4 VP3 binds to lipid vesicles of different compositions and net charge: zwitterionic, anionic, and cationic. 32,33 Vesicles incorporating MAP 4 VP3 can increase the immunogenic response both by increasing circulation time of the peptide in blood and protecting it from degradation by lytic enzymes 34 and by favoring delivery of the immunopeptide to target cells of the immune system. However, although the stoichiometry of binding is approximately the same (14 -16 lipid molecules per peptide) for all three types of vesicles, independent of the charge, the bound forms have different activity.…”

Section: Probementioning

confidence: 99%

Fluorescence study on the interaction of a multiple antigenic peptide from hepatitis A virus with lipid vesicles

Ortiz¹,

Cajal²,

Haro³

et al. 2000

Biopolymers

View full text Add to dashboard Cite

The interaction of the multiple antigenic peptide MAP4VP3 with lipid membranes has been studied by spectroscopic techniques. MAP4VP3 is a multimeric peptide that corresponds to four units of the sequence 110-121 of the capsid protein VP3 of hepatitis A virus. In order to evaluate the electrostatic and hydrophobic components on the lipid-peptide interaction, small unilamelar vesicles of different compositions, including zwitterionic dipalmitoylphosphatidylcholine (DPPC), anionic dipalmitoylphosphatidylcholine/phatidylinositol (DPPC:PI 9:1), and cationic dipalmitoylphosphatidylcholine/stearylamine (DPPC:SA 9.5:0.5), were used as membrane models. Intrinsic tryptophan fluorescence changes and energy transfer experiments show that MAP4VP3 binds to all three types of vesicles with the same stoichiometry, indicating that the electrostatic component of the interaction is not important for binding of this anionic peptide. Steady-state polarization experiments with vesicles labeled with 1,6-diphenyl-1,3,5-hexatriene or with 1-anilino-8-naphtalene sulphonic acid indicate that MAP4VP3 induces a change in the packing of the bilayers, with a decrease in the fluidity of the lipids and an increase in the temperature of phase transition in all the vesicles. The percentage of lipid exposed to the bulk aqueous phase is around 60% in intact vesicles, and it does not change upon binding of MAP4VP3 to DPPC vesicles, indicating that the peptide does not alter the permeability of the membrane. An increase in the amount of lipid exposed to the aqueous phase in cationic vesicles indicates either lipid flip-flop or disruption of the vesicles. Binding to DPPC vesicles occurs without leakage of entrapped carboxyfluorescein, even at high mol fractions of peptide. However, a time-dependent leakage is seen with cationic DPPC/SA and anionic DPPC/PI vesicles, indicating that the peptide induces membrane destabilization and not lipid flip-flop. Resonance energy transfer experiments show that MAP4VP3 leakage from cationic vesicles is due to membrane fusion, whereas leakage from anionic vesicles is not accompanied by lipid mixing. Results show that MAP4VP3 interacts strongly with the lipid components of the membrane, and although binding is not of electrostatic nature, the bound form of the peptide has different activity depending on the membrane net charge; thus, it is membrane disruptive in cationic and anionic vesicles, whereas no destabilizing effect is seen in DPPC vesicles.

show abstract

Parameters affecting the immunogenicity of a liposome‐associated synthetic hexapeptide antigen

Cited by 45 publications

References 38 publications

Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

Liposomes: from membrane models to gene therapy

Fluorescence study on the interaction of a multiple antigenic peptide from hepatitis A virus with lipid vesicles

Contact Info

Product

Resources

About