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Maturation of Aluminium Adsorbed Antigens Contributes to the Creation of Homogeneous Vaccine Formulations.

作者信息

Laera Donatello, Scarpellini Camilla, Tavarini Simona, Baudner Barbara, Marcelli Agnese, Pergola Carlo, Meppen Malte, O'Hagan Derek T

机构信息

Technical & Research Development, Drug Product, GSK, 53100 Siena, Italy.

Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

出版信息

Vaccines (Basel). 2023 Jan 11;11(1):155. doi: 10.3390/vaccines11010155.


DOI:10.3390/vaccines11010155
PMID:36680000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9862877/
Abstract

Although aluminium-based vaccines have been used for almost over a century, their mechanism of action remains unclear. It is established that antigen adsorption to the adjuvant facilitates delivery of the antigen to immune cells at the injection site. To further increase our understanding of aluminium-based vaccines, it is important to gain additional insights on the interactions between the aluminium and antigens, including antigen distribution over the adjuvant particles. Immuno-assays can further help in this regard. In this paper, we evaluated how established formulation strategies (i.e., sequential, competitive, and separate antigen addition) applied to four different antigens and aluminium oxyhydroxide, lead to formulation changes over time. Results showed that all formulation samples were stable, and that no significant changes were observed in terms of physical-chemical properties. Antigen distribution across the bulk aluminium population, however, did show a maturation effect, with some initial dependence on the formulation approach and the antigen adsorption strength. Sequential and competitive approaches displayed similar results in terms of the homogeneity of antigen distribution across aluminium particles, while separately adsorbed antigens were initially more highly poly-dispersed. Nevertheless, the formulation sample prepared via separate adsorption also reached homogeneity according to each antigen adsorption strength. This study indicated that antigen distribution across aluminium particles is a dynamic feature that evolves over time, which is initially influenced by the formulation approach and the specific adsorption strength, but ultimately leads to homogeneous formulations.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/aceed0750ec9/vaccines-11-00155-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/8421f6feef2c/vaccines-11-00155-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/990745a37c5f/vaccines-11-00155-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/c062fe1ebc9f/vaccines-11-00155-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/f514bdbe79b3/vaccines-11-00155-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/0a1513536827/vaccines-11-00155-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/3a913b8e89ae/vaccines-11-00155-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/032b03f825b9/vaccines-11-00155-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/fe9e4a07e2d1/vaccines-11-00155-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/aceed0750ec9/vaccines-11-00155-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/8421f6feef2c/vaccines-11-00155-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/990745a37c5f/vaccines-11-00155-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/c062fe1ebc9f/vaccines-11-00155-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/f514bdbe79b3/vaccines-11-00155-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/0a1513536827/vaccines-11-00155-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/3a913b8e89ae/vaccines-11-00155-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/032b03f825b9/vaccines-11-00155-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/fe9e4a07e2d1/vaccines-11-00155-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763e/9862877/aceed0750ec9/vaccines-11-00155-g009.jpg

相似文献

[1]
Maturation of Aluminium Adsorbed Antigens Contributes to the Creation of Homogeneous Vaccine Formulations.

Vaccines (Basel). 2023-1-11

[2]
The in vitro displacement of adsorbed model antigens from aluminium-containing adjuvants by interstitial proteins.

Vaccine. 1999-7-16

[3]
Nanoalum adjuvanted vaccines: small details make a big difference.

Semin Immunol. 2021-8

[4]
Structural perturbation of diphtheria toxoid upon adsorption to aluminium hydroxide adjuvant.

Vaccine. 2012-9-18

[5]
Quantitative Analysis of Vaccine Antigen Adsorption to Aluminum Adjuvant Using an Automated High-Throughput Method.

PDA J Pharm Sci Technol. 2018

[6]
Spectroscopic characterization of antibodies adsorbed to aluminium adjuvants: correlation with antibody vaccine immunogenicity.

Vaccine. 2005-2-25

[7]
Engineering the hydroxyl content on aluminum oxyhydroxide nanorod for elucidating the antigen adsorption behavior.

NPJ Vaccines. 2022-6-23

[8]
Atomic-Scale Description of Interfaces between Antigen and Aluminum-Based Adjuvants Used in Vaccines by Dynamic Nuclear Polarization (DNP) Enhanced NMR Spectroscopy.

Chemistry. 2020-7-8

[9]
[Adsorption of antigens K88 and K99 on aluminum hydroxide gel].

Vet Med Nauki. 1987

[10]
NaCl strongly modifies the physicochemical properties of aluminum hydroxide vaccine adjuvants.

Int J Pharm. 2017-1-30

引用本文的文献

[1]
New High-Throughput Method for Aluminum Content Determination in Vaccine Formulations.

Vaccines (Basel). 2025-1-22

[2]
PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies.

Hum Vaccin Immunother. 2025-12

[3]
Analysis of immunogenicity and purification methods in conjugated polysaccharide vaccines: a new approach in fighting pathogenic bacteria.

Front Immunol. 2024-11-20

[4]
Analytical Insights into Protein-Alum Interactions and Their Impact on Conformational Epitope.

Pharmaceutics. 2024-3-19

[5]
Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

Vaccine. 2023-10-20

[6]
Aluminum Adjuvants-'Back to the Future'.

Pharmaceutics. 2023-7-4

[7]
Nanoalum Formulations Containing Aluminum Hydroxide and CpG 1018 Adjuvants: The Effect on Stability and Immunogenicity of a Recombinant SARS-CoV-2 RBD Antigen.

Vaccines (Basel). 2023-5-26

[8]
Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

bioRxiv. 2023-4-4

本文引用的文献

[1]
Analytical and Preformulation Characterization Studies of Human Papillomavirus Virus-Like Particles to Enable Quadrivalent Multi-Dose Vaccine Formulation Development.

J Pharm Sci. 2022-11

[2]
Fundamental Principles of the Thermodynamics and Kinetics of Protein Adsorption to Material Surfaces.

Colloids Surf B Biointerfaces. 2020-7

[3]
Adsorption onto aluminum hydroxide adjuvant protects antigens from degradation.

Vaccine. 2020-4-23

[4]
Impact of Formulation and Suspension Properties on Redispersion of Aluminum-Adjuvanted Vaccines.

J Pharm Sci. 2020-4

[5]
Simultaneous visualization and quantitation of dual antigens adsorbed on adjuvants using high content analysis.

Nanomedicine (Lond). 2019-10-11

[6]
Effect of Aluminum Adjuvant and Preservatives on Structural Integrity and Physicochemical Stability Profiles of Three Recombinant Subunit Rotavirus Vaccine Antigens.

J Pharm Sci. 2020-1

[7]
Towards animal free and science based measures of critical quality attributes for vaccine quality control and release.

Vaccine. 2019-6-27

[8]
Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach.

Int J Nanomedicine. 2018-6-26

[9]
Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

PLoS One. 2018-5-29

[10]
Principles of vaccine potency assays.

Bioanalysis. 2018-2

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