Understanding and manipulating chemokines and their receptors in the context of adjuvants

All vaccines contain components called 'adjuvants' that boost the immune response and enhance vaccine-induced protection. Different adjuvants can also select the type of response that develops, with the appropriate type of response inducing disease protection, whereas inappropriate responses may cause increased susceptibility to infection. Despite this crucial role for adjuvants in vaccine development, the reasons why certain vaccine adjuvants and/or delivery systems are more or less effective at inducing immune responses or promoting the preferential induction of particular types of response are unknown. It appears that the number, type and persistence of the cells of the immune system that underlie vaccine responses (lymphocytes) may be an important determinant of how effective a vaccine is. Thus understanding the factors that control immune cell behaviour will clearly make a significant contribution to the rational design of vaccines. We propose that the molecules regulating the movement of the cells of the immune system, namely chemokines and their receptors, orchestrate these processes and furthermore, appropriate modulation of chemokines will enhance adjuvant and consequently vaccine efficacy. These studies are of a basic biological nature, however we believe they will open up new avenues in vaccine adjuvant research, and provide a rational framework for the application of chemokines and manipulation of cellular movement in vaccine development.

The reasons why certain vaccine adjuvants and/or delivery systems are more or less effective at inducing immune responses or promoting the preferential induction of particular types of response are unknown. However, identifying the factors that determine the induction, magnitude, phenotype and persistence of lymphocyte responses to antigenic challenge will clearly make a significant contribution to the rational design of vaccines. Central to the function of vaccines is the role of adjuvants. These agents are believed to enhance the uptake, transport and availability of antigen to the immune system. We propose that the molecules regulating the movement of the cells of the immune system, namely chemokines and their receptors, orchestrate these processes and that their modulation could enhance adjuvant and consequently vaccine efficacy. Thus understanding how chemokines impact on the induction of adaptive immune responses is a fundamental immunological objective that has significant implications in the management of animal and human health. In particular, this has relevance to use of vaccines in commercial animals and also the ageing human population where vaccines have reduced efficacy.

Communications and Engagement We have a strong track record of Public Engagment in the area of vaccines and immunology. These activities have included; the Edinburgh International Science Festival, contributions to a BBC Radio Scotland series on Vaccination, talks to local societies (e.g. Ayr Photographic Society) and primary and secondary schools (e.g. Mearns Primary, Renfrew High School). We have recently participated in a school's open day organised by Medical Research Scotland, to encourage children from challenging backgrounds to consider science as a career. We have also organised public engagement in science events as part of meetings of the Scottish Immunology Group (a regional group of the British Society for Immunology). We have also had a number of high profile imaging discoveries carried by the national (e.g. The Times, The Herald) and scientific press (e.g. Science). We intend to continue these activities as the types of data generated in this proposal are not only scientifically important, but also our imaging studies are visually stimulating and accessible to a lay audience. Exploitation and Application We also have a track record of engagement with the Pharmaceutical and Biotechnology sectors. All of the applicants have participated in one or more of; commercialisation of products (Brewer, Variation Biosciences; Graham, Novartis), establishment of spin out companies (Garside, MD Biosciences); delivery of industrially sponsored projects (Garside/Brewer, AstraZeneca), collaborations with major pharmaceutical companies (Garside/Brewer, Astra Zeneca; Garside, Bristol Myers Squibb) or commercial consultation (Brewer, Proteus Molecular Design). Through these interactions and experience, we feel there will be ample opportunity for interaction and training with industrial partners and the investigation of the commercial potential of our findings. Capability All of the applicants are strongly committed to the ideals of public engagement and commercial development in their research projects. We will continue to develop our activities in this area and will continue to include these aspects within the training environment that we have created for our Postdoctoral and Graduate Research Assistants and Students.