Award details

Understanding the maintenance of protective antibody titres in cattle

Reference	BBS/E/I/00001447
Principal Investigator / Supervisor	Professor Bryan Charleston
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	1,613,683
Status	Completed
Type	Institute Project
Start date	01/07/2009
End date	31/03/2012
Duration	33 months

Abstract

CD4 T cell assays have been developed and when combined with serological assays provide some correlation with protection and an association with prolonged duration of immunity. However, there are also examples where protection and maintenance of protective neutralising antibody titres post-vaccination is not associated with an easily detectable CD4 T cell response most notably after natural infection. We have recently demonstrated the long term retention of FMDV antigen in lymphoid tissue, this depot of antigen may play a key role in maintaining neutralising antibody titres after infection. The assays to measure CD4 T cell responses will be further refined to improve the specificity of the correlation with protection including using Multiparameter flow cytometry to measure intracellular cytokines and intracellular CD154. It is clear that apart from adjuvants, which operate by multiple mechanisms, persistence of antigen is an important factor in the maintenance of immune responses. The role of antigen present on follicular DCs will be investigated by using lymphotoxin ß receptor immunoglobulin fusion protein to disrupt FDC networks and associated antigen depots. Assays to quantify the memory B cell response will be adapted for use after FMDV infection and vaccination in cattle. The capacity to measure the frequency of plasma cells and memory B cells will significantly improve the ability to assess the potential of a vaccine to induce a long term serological response. In addition, using a mouse model of FMDV infection, improved assays will be developed to measure correlates of protection for FMDV in cattle. The importance of long-term retention of FMDV antigen, in germinal centres of lymphoid tissue after infection, in the maintenance of a high titre serological response will be studied. We aim to determine the influence of capsid stability on duration of protective immunity.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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