Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715610
Title: Native outer membrane vesicles as vaccine candidates against neisseria meningitidis
Author: Marini, Arianna
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Thesis embargoed until 01 Jun 2023
Access from Institution:
Abstract:
An affordable vaccine against all serogroups of Neisseria meningitidis causing reoccurring epidemics in sub-Saharan Africa is needed. Native outer membrane vesicles (NOMV) with over-expressed factor H binding protein (fHbp) represent a promising vaccine approach. We investigated the contribution of fHbp variant 1 amino acidic sequence to the cross-reactivity of the antibody response generated by NOMV OE fHbp. Coupling structure-sequence analysis of fHbp with epidemiological data of meningococcal prevalence in Africa, we selected four fHbp v.1 IDs (1, 5, 9, 74), to generate isogenic mutants of a serogroup W African isolate, over-expressing each of the them. NOMV from the mutants were purified, characterized, and the antibody response generated in mice was investigated, and compared to the corresponding recombinant fHbp. This is the first study indicating that the amino acid sequence of fHbp influences the specificity of the antibody response generated, not only as recombinant protein, but also when over-expressed on NOMV. In mice NOMV OE fHbp induced a fast, long-lasting antibody response, with high IgM and IgG antibody levels 7 days after immunization, and germinal centers induced. LipidA modifications do not impact primary antibody response, while precipitation of the antigen on alum attenuated the early antibody response, but enhance its longevity.
Supervisor: Not available Sponsor: People Programme (Marie Curie Actions) ; GSK Vaccines Institute for Global Health ; University of Birmingham
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.715610  DOI: Not available
Keywords: QH301 Biology ; QH426 Genetics ; QR180 Immunology
Share: