Refining an in vitro system of predictive biomarkers of in vivo liposome efficacy

Adjuvants, essential components of subunit vaccines, are capable of eliciting strong protective responses in vivo. However, Alum-based adjuvants (used in humans) fail to promote protective immune responses as they induce weak Th1/CTL responses and are not applicable to the control of important intracellular infections such as TB, HIV and malaria.

Liposomes are at the forefront of vaccine design as they can both deliver antigen and exert adjuvant effects. However a major challenge to vaccine development is our ability to predict which liposome formulations will demonstrate in vivo efficacy. Novel formulations tend to be incremental developments of existing formulations and rely heavily on animal tests from an early stage. Our ultimate goal is to allow liposome formulation library screens to replace animal use at early formulation testing and reduce regulatory-required animal use through testing of only the most promising leads.

We have successfully established in vitro models of antigen presenting cells (APC) and in vitro tests of APC function that permit discrimination of highly effective from ineffective liposome formulations. Here we will assess our panel of tests against a broader range of formulations with a greater distribution of in vivo efficacy, and optimize the panel of tests to predict both the extent and nature (e.g. Th1/2/17) of an in vivo immune response that will be induced.

Within this programme we will continue to use Aston’s extensive bank of existing in vivo data from a broad range of liposome formulations. We will develop further our test panel through the incorporation of multiplex cytokine analyses and will assess the in vitro APC responses to a range of liposome fomulations including, for the first time, those of intermediate in vivo efficacy.

Our work will define an adjuvant library screening approach to speed the development of novel liposome antigen delivery/adjuvant systems without the need for animals in early stage testing.

Nguyen DB et al. (2016). Characterization of Microvesicles Released from Human Red Blood Cells. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology 38(3):1085-99. doi: 10.1159/000443059

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PhD Studentship




Aston University

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Award date

Oct 2016 - Sep 2019

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