Adsorption of protein antigen to the cationic liposome adjuvant CAF®01 is required for induction of Th1 and Th17 responses but not for antibody induction

Adjuvants have been used for decades to enhance the immune response to vaccines, in particular for the subunit-based adjuvants. Physicochemical properties of the adjuvant-protein antigen complexes, such as size, morphology, protein structure and binding, influence the overall efficacy and safety of the vaccine. Here we show how to perform an accurate physicochemical characterization of the nanoaluminum–ovalbumin complex. Using a combination of existing techniques, we developed a multi-staged characterization strategy based on measurements of increased complexity. This characterization cascade has the advantage of being very flexible and easily adaptable to any adjuvant-protein antigen combinations. It will contribute to control the quality of antigen–adjuvant complexes and immunological outcomes, ultimately leading to improved vaccines.

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Design and immunological properties of topographic immunogenic determinants of a protein antigen (LDH-C4) as vaccines.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)42700-7 ◽

1992 ◽

Vol 267 (9) ◽

pp. 6338-6346

Author(s):

P.T. Kaumaya ◽

A.M. VanBuskirk ◽

E Goldberg ◽

S.K. Pierce

Keyword(s):

Protein Antigen ◽

Immunological Properties

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Mechanism of Thimerosal-Induced Structural Destabilization of a Recombinant Rotavirus P[4] Protein Antigen Formulated as a Multi-Dose Vaccine

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2020.11.033 ◽

2020 ◽

Author(s):

Kawaljit Kaur ◽

Jian Xiong ◽

Nishant Sawant ◽

Sanjeev Agarwal ◽

John M. Hickey ◽

...

Keyword(s):

Protein Antigen ◽

Dose Vaccine

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Interleukin-2 receptor antibody induction with early low dose tacrolimus preserves post-liver transplant renal function in at risk individuals

Journal of Liver Transplantation ◽

10.1016/j.liver.2021.100028 ◽

2021 ◽

pp. 100028

Author(s):

Jeremy S Nayagam ◽

Oliver D Tavabie ◽

Benjamin Norton ◽

Michael JS McMahon ◽

Katie Ramos ◽

...

Keyword(s):

At Risk ◽

Renal Function ◽

Liver Transplant ◽

Low Dose ◽

Interleukin 2 ◽

Receptor Antibody ◽

Interleukin 2 Receptor ◽

Antibody Induction

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Paclitaxel loading in cationic liposome vectors is enhanced by replacement of oleoyl with linoleoyl tails with distinct lipid shapes

Scientific Reports ◽

10.1038/s41598-021-86484-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuhong Zhen ◽

Kai K. Ewert ◽

William S. Fisher ◽

Victoria M. Steffes ◽

Youli Li ◽

...

Keyword(s):

Clinical Trials ◽

Membrane Structure ◽

Cationic Liposome ◽

Solubility Limit ◽

Loading Capacity ◽

Prostate Cancer Cells ◽

X Ray ◽

X Ray Scattering ◽

Cylindrical Micelles ◽

Molecular Affinity

AbstractLipid carriers of hydrophobic paclitaxel (PTX) are used in clinical trials for cancer chemotherapy. Improving their loading capacity requires enhanced PTX solubilization. We compared the time-dependence of PTX membrane solubility as a function of PTX content in cationic liposomes (CLs) with lipid tails containing one (oleoyl; DOPC/DOTAP) or two (linoleoyl; DLinPC/newly synthesized DLinTAP) cis double bonds by using microscopy to generate kinetic phase diagrams. The DLin lipids displayed significantly increased PTX membrane solubility over DO lipids. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the solubility limit, which has been the focus of most previous studies and clinical trials) in DOTAP/DOPC CLs. The increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX, rather than by the transition in membrane structure from bilayers to inverse cylindrical micelles observed with small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against prostate cancer cells (their IC50 of PTX cytotoxicity) was unaffected by changing the lipid tails, and toxicity of the CL carrier was negligible. Moreover, efficacy was approximately doubled against melanoma cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. Our findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.

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