High-Throughput Discovery of Novel Nanoparticulate Vaccine Adjuvants for Humans

This project seeks to develop new additives for vaccines using a mutidisciplinary approach comprising a mixture of experimental and in silico research.

Vaccination saves 3 million lives annually through the induction of protective immunity to infection. Modern vaccines commonly contain a chemical known as an "adjuvant", which is needed to deliver effective immunity. "Alum" is often used as an adjuvant: it provokes strong immunity against bacterial toxins, but cannot stimulate the type of immune response required to eliminate virally infected cells or cancers. This project will build on recent work by UCL researchers and develop advanced alum adjuvants to solve these problems.

The major constituent of alum is commonly AlOOH. The project will exploit a novel and green route to the preparation of AlOOH via the use of flow reactors. In these reactors, we can generate AlOOH with precise control over the size and shape of the particles. We will prepare a large series of different AlOOH and doped AlOOH materials with varied particle size, shape and composition. Their adjuvanticity will then be assessed, and mathematical models will be developed to correlate the immune response produced with the properties of the AlOOH sample.

The research will provide further understanding of the factors governing the immunogenicity of vaccine adjuvants and their mechanisms of action. It should also lead to the identification of new adjuvants with potential use in the prevention of cancer and viral infections. The ultimate goal of this work is for the models developed to be used for the in silico screening of very large numbers of materials. This should permit the identification of suitable adjuvants to drive the desired immune response for a particular vaccine. It will allow the number of lab animals used in vaccine development to be reduced significantly, and could lead to new, more effective, vaccines – and thus to the saving and improvement of countless lives.

A wide range of AlOOH samples will initially be prepared using flow reactors and their immunological properties will be explored using in vitro assays on human dendritic cells. Mathematical models will be developed to link AlOOH physicochemical properties to the observed immune responses. Subsequently, the project will aim to develop low-cost screening assays using cell lines. Doped AlOOH samples will also be prepared and their immunological properties studied. Lead candidates will be taken forward into in vivo studies through collaboration.

Supervisors
Dr Gareth Williams (UCL SOP) / Prof Jawwad Darr (UCL Chemistry)
http://iris.ucl.ac.uk/iris/browse/profile?upi=GWILL02

The successful applicant will be expected to have a UK Bachelor’s degree in Pharmacy, Chemistry, Biochemistry, Chemical Engineering, Materials Science or Immunology, awarded with first or upper second-class Honours, or an overseas qualification of an equivalent standard from a recognised higher education institute, or a recognised taught Master’s degree is required.

Applications must include a CV, personal statement, and the contact details of two referees. They should be sent to Victor Diran ([Email Address Removed]).