Immune responses to prototype GMMA vaccine against Neisseria meningitidis in Africa

Ispasanie, Emma Helena Berta (2015). Immune responses to prototype GMMA vaccine against Neisseria meningitidis in Africa. University of Birmingham. Ph.D.

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Abstract

\(Neisseria\) \(meningitides\) is a major cause of meningitis epidemics in sub-Saharan Africa. A promising broadly-protective vaccine approach is outer membrane particle-based vaccine comprising GMMA (Generalised Modules for Membrane Antigens). To better understand vaccine potential and immune responses induced by GMMA, we (i) typed outer membrane vaccine antigens fHbp, NadA, NHBA and PorA in African serogroup A, W and X isolates, (ii) produced GMMA from recombinant strains expressing fHbp variant 1 or NadA-3, and (iii) generated and characterised monoclonal antibodies (mAb) against GMMA.

Characterisation of 94 isolates showed limited variability of fHbp, NadA and PorA over time and geographical region. Mice immunised with GMMA developed cross-reactive bactericidal antibody responses against diverse serogroup A, W and X isolates that targeted fHbp, NadA and other unidentified antigens. We obtained 33 hybridoma clones producing GMMA-binding mAbs. Four mAbs of immunoglobulin subclasses IgG1, IgG2a/b and IgG3 bound NadA and four IgG1 mAbs bound fHbp. The other 25 mAbs recognised seven other antigens. In bactericidal assays all anti-NadA mAbs killed the vaccine serogroup A strain. Five mAbs against unknown antigens also showed bactericidal activity against another A isolate. Conclusively, the results provide support for developing a GMMA-based vaccine with broad coverage against meningococcal meningitis for Africa.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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