Development of a rapid in vitro pre-screen for distinguishing effective liposome-adjuvant delivery systems

Laura A. J. Feather, Vinod Nadella, Elisabeth Kastner, Yvonne Perrie, Anthony C. Hilton, Andrew Devitt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Liposomes are a strong supporting tool in vaccine technology, as they are a versatile system that not only act as antigen delivery systems but also adjuvants that can be highly effective at stimulating both innate and adaptive immune responses. Their ability to induce cell-mediated immunity makes their use in vaccines a useful tool in the development of novel, more effective vaccines against intracellular infections (e.g. HIV, malaria and tuberculosis). Currently, screening of novel liposome formulations uses murine in vivo models which generate data that often correlates poorly with human data. In addition, these models are both high cost and low throughput, making them prohibitive for large scale screening of formulation libraries. This study uses the cationic liposome formulation DDA:TDB (known as cationic adjuvant formulation 01 (CAF01)), as a lead formulation, along with other liposome formulations of known in vivo efficacy to develop an in vitro screening tool for liposome formulation development. THP-1-derived macrophages were the model antigen presenting cell used to assess the ability of the liposome formulations to attract, associate with and activate antigen presenting cells in vitro, crucial steps necessary for an effective immune response to antigen. By using a combination of in vitro functions, the study highlights the potential use of an in vitro screening tool, to predict the in vivo efficacy of novel liposome formulations. CAF01 was predicted as the most effective liposome formulation when assessing all in vitro functions and a measure of in vitro activation was able to predict 80% of the liposome correctly for their ability to induce an in vivo IFN-ү response.

Original languageEnglish
Article number12448
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 20 Jul 2022

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Funding: We gratefully acknowledge the support of NC3R for funding AD, YP and ACH for this research (NC/N002466/1).

Keywords

  • Adjuvants, Immunologic/pharmacology
  • Adjuvants, Pharmaceutic
  • Animals
  • Antigens
  • Cations
  • Humans
  • Immunity, Humoral
  • Liposomes
  • Mice
  • Quaternary Ammonium Compounds
  • Vaccines

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