Lindsay, R.W.B.; (2005) Characterisation of lymphocyte migration following DNA vaccination. Doctoral thesis , University of London.

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Abstract

Infection with influenza virus generally produces an immune response in immunocompetent individuals that will protect from further infection of the same strain of virus. The experiments carried out in this study were designed to identify correlates of protection induced by primary experimental influenza virus infection and to compare to/and assess Particle Mediated Immunotherapeutic Delivery (PMID) as a method of DNA immunisation. Initial experiments characterised the protective immune response observed following intranasal influenza virus infection with regard to the humoral and cellular responses generated. It became clear that a combination of systemic and mucosal antibody responses and strong virus-specific CD8+ T cell response in the lungs were important in the control of viral replication. The data on the immune responses generated following influenza virus infection was used as a "gold standard" to compare the responses observed following PMID immunisation of influenza virus nucleoprotein (NP) DNA. When PMID was assessed for its ability to generate an immune response, a mucosal immune response was observed in the D-NALT as well as a more general systemic response. Whilst a single immunisation induced specific cellular responses, it proved inefficient at generating a humoral response. Protection studies showed that priming by PMID of NP DNA, resulted in a level of protection that reduced viral replication in the lungs by 2 logs. Investigation into the phenotype of virus-specific T cells generated by either infection or immunisation showed that they have a common CD44hiCD11ahlCD62L10 phenotype in various systemic and mucosal tissues. The cells isolated from the D-NALT displayed an intriguing intermediate level of CD44 expression. In vivo migration studies showed a tendency for activated splenic virus-specific CD8+ T cells to home to the D-NALT perhaps implying a role for the D-NALT as a site where effector/memory T cells actively home as part of their role in immune surveillance.

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