Oxford Martin Programme: Vaccines to Tackle Variable Pathogens

Cluster Co-leaders: Prof Adrian Hill, Prof Andrew Pollard and Prof Christoph Tang

Cluster Investigators: Prof Ellie Barnes, Prof Sarah Gilbert, Prof Sunetra Gupta, Prof Susan Lea, Prof Martin Maiden, Dr Arturo Reyes-Sandoval, Prof Julian Savulescu, Dr Adrian Smith, Dr David Wyllie

Podcast:Oxford Martin Seminar 28th Nov 2013: Developing effective and equitable global health systems

Combating variable pathogens through new-generation vaccines would prevent globally important diseases such as pandemic influenza, dengue, malaria and hepatitis C and major UK diseases such as methicillin-resistant Staphylococcus aureus (MRSA) and Group B Neisseria meningitidis (meningitis B).

We aim here to integrate improved vaccine design with new needle-free delivery technologies. To enhance the public health impact of immunisations we will also endeavour to combine improvements in vaccine design with an improved ethical framework responsive to the regulatory and societal questions raised by new vaccination approaches.

Interdisciplinary approaches to vaccine development

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The Oxford Martin School is a unique, interdisciplinary research community of over 300 scholars working to address the most pressing global challenges and opportunities of the 21st century.

The school supports over 30 individual research teams from across the University of Oxford who aim to have a significant impact beyond academia and to make a tangible difference to any of today’s significant global challenges. 'Vaccines to Tackle Variable Pathogens' is a Programme which aims to bring together leading experts from six departments and three divisions of the University of Oxford within the following three research approaches:

1. Conserved Genomic Regions Approach Groups involved: Prof Ellie Barnes, Prof Sarah Gilbert, Prof Sunetra Gupta, Prof Adrian Hill, Arturo Reyes-Sandoval. Departments: Medicine, Zoology

2. Multi-Allelic Approach Groups involved: Prof Susan Lea, Prof Sarah Gilbert, Prof Sunetra Gupta, Prof Andrew Pollard, Dr Adrian Smith, Prof Christoph Tang. Departments: Pathology, Paediatrics, Zoology, Medicine

3. Novel Vaccine Delivery Approach Groups involved: Prof Andrew Pollard, Prof Julian Savulescu, Dr David Wyllie. Departments: Paediatrics, Medicine, Engineering Science, Philosophy

We will evaluate two new approaches for designing antigenic components of new vaccines: (1) the use of conserved genomic segments, and (2) generation of multi-allelic vaccines. In the ‘conserved genomic’ approach we will use bioinformatic tools to identify conserved segments from pathogenic subtypes of bacteria, viruses and parasites to generate new vaccine antigens. This approach has been successfully applied to HIV and we will use this tailored design for new vaccines against dengue, HCV, and influenza. In the ‘multi-allelic approach’ we will use population genetic, theoretical, and bioinformatic evidence of immune selection, atomic level structural information, and functional analysis of protective antigens to develop multi-allelic vaccine candidates. Combining antigen variants in such ‘cocktail’ vaccines against N. meningitidis, influenza and malaria should achieve greater coverage of disease associated strains and we shall evaluate these constructs for improved immunogenicity and efficacy.

We will complement these inter-disciplinary antigen design strategies with a new molecular approach to improved antigen delivery. Selected “framework” proteins will be used as a scaffold into which multiple antigenic loops can be readily fused genetically to provide an efficient system for delivering disease-specific antigens in an immunogenic form. This exciting technology provides a platform for rapidly generating vaccines against newly emerging pathogens. Parallel to this we will aim to improve vaccine administration with a bioengineering approach using antigen-loaded nanoparticles for needle-free vaccine delivery.

Thirdly, we will address critical societal obstacles to wider vaccine acceptability. We will examine novel ethical issues associated with the use of vaccines against variable pathogens, including the ethics of deploying vaccines with limited efficacy, and aspects of distributive justice associated with pathogen strain selection.