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Title: Investigating primary and secondary B cell responses in cattle after immunisation with existing and novel vaccines
Author: Grant, Clare F. J.
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2013
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Antibodies play a pivotal role in protecting against viral infection, maintenance of this protective response is provided by plasma and memory B cells. Foot and mouth disease virus (FMDV) is a highly contagious pathogen and studies in cattle have shown that protection from the virus is antibody-mediated. However, FMDV vaccines are unable to achieve long durations of immunity. Therefore, understanding the FMDV-specific B cell responses in cattle is essential to inform future vaccine design. Antigen-specific ELIspot assays were used to determine the kinetics of the bovine B cell response to T-dependent and -independent antigens. An ELIspot assay was developed to allow enumeration of FMDV-specific plasma and memory B cells following vaccination and live-virus challenge. In addition, a novel surgical technique was also developed to allow enumeration of antigen-specific B cells when exiting a regional lymph node, following vaccination. The bovine immunoglobulin repertoire was investigated at the peak of the B cell responses using deep sequencing. T-dependent B cell responses in cattle were characterised by a small burst of antigen- specific plasma cells occurring after the primary vaccination, which was coupled with an increase in antigen-specific IgG titres. In keeping with the central dogma of immunolog- ical priming, the plasma cell burst post booster vaccination was larger and more rapid. Antigen-specific memory B cells were detectable for over 6 months. In contrast, immu- nisation with a T-independent antigen resulted in no detectable plasma or memory B cells. Vaccination with inactivated FMDV, novel FMDV antigens and live-virus chal- lenge induced in a burst of FMDV-specific plasma cells but low numbers of memory B cells. Deep sequencing of immunoglobulin transcripts at the peak of the antigen-specific plasma cell response post vaccination, detected increases in bovine IgG transcripts in both blood and efferent lymph following booster vaccination, indicating that they are likely to be FMDV-specific. Deep sequencing has also revealed that cattle exhibit a broad range of heavy chain CDR3 lengths and highly similar light-chain transcripts that are shared between animals. Overall, this data suggests that the kinetics of the bovine plasma and memory B cell response to antigen is similar to that demonstrated in humans and mice. However, the bovine antibody V region structure is different and is likely to interact with its cognate antigen differently.
Supervisor: Pollard, Andrew Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biology ; Immunology ; Vaccination ; foot-and-mouth disease virus ; B cell ; bovine