Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.700136
Title: Immune responses induced by Mycobacterium bovis BCG, and modified vaccinia virus Ankara expressing mycobacterial antigen 85A, when delivered as mucosal or systemic vaccinations to non-human primates
Author: White, Andrew David
ISNI:       0000 0004 5991 9441
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2016
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Abstract:
Vaccination is the most effective way to control a global disease such as tuberculosis (TB); however, conventional intradermal (ID) injection of the licensed TB vaccine, BCG, provides only limited protection. Mucosal delivery of vaccines to pulmonary surfaces is a loqical approach to generate a protective immune response at the primary site of infection. Non-human primate (NHP) models have been used to compare the safety and immunogenicity of mucosal and ID TB vaccination strategies using BCG and modified vaccinia virus Ankara expressing TB antigen 85A (MVA85A). Mucosal vaccination strategies were well tolerated and induced potent antigen-specific CD4 and CD8 T-cell responses, including polyfunctional T-cells in the lung and peripheral immune compartment. Systemic immune responses induced by mucosal BCG revaccination and MVA85A boost vaccination were relatively transient, whereas antigen-specific responses detected in mucosal tissues and bronchoalveolar lavage (BAL) samples were more persistent. Unlike ID vaccination, aerosol vaccination with MVA85A did not induce a detectable serum anti-vector antibody response. Polyfunctional CD4 T-cells were detected in BAL and peripheral blood mononuclear cells (PBMC) following aerosol and ID BCG vaccination. The immunogenicity of aerosol-delivered BCG was dose dependent and consisted of both Th 1 and Th 17 cytokine responses. The aerosol BCG-induced T -cell response measured in BAL and PBMC was significantly delayed relative to ID-vaccination, with a similar trend apparent in serum anti-PPD IgG levels. Mucosal CD4 and CD8 populations were polarised toward an effector memory phenotype, whereas frequencies of peripheral central memory T-cells increased significantly, and remained elevated, following aerosol vaccination. Expression of the 04131 integrin lung homing markers remained consistently high on C04 and C08 T-cells isolated from BAL, and varied on peripheral T -cells. These studies indicate, that delivery of TB vaccines to the pulmonary surfaces is practical and safe, with the potential to target the cell-mediated immune response to the lung. The comparison of aerosol and ID BCG vaccination highlighted differences in the mycobacteria-specific immune response that may contribute to the enhanced protection previously reported from aerosol BCG studies, and will inform future investigations of mucosal TB vaccination strategies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.700136  DOI: Not available
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