Interrogation of human monoclonal antibodies induced by 4C-MenB to identify protective antigens contained in the OMV component

Vezzani, Giacomo (2022) Interrogation of human monoclonal antibodies induced by 4C-MenB to identify protective antigens contained in the OMV component, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare, 34 Ciclo. DOI 10.48676/unibo/amsdottorato/10072.
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Neisseria meningitidis is a gram negative human obligated pathogen, mostly found as a commensal in the oropharyngeal mucosa of healthy individuals. It can invade this epithelium determining rare but devastating and fast progressing outcomes, such as meningococcal meningitidis and septicemia, leading to death (about 135000 per year worldwide). Conjugated vaccines for serogroups A, C, W135, X and Y were developed, while for N. meningitidis serogroup B (MenB) the vaccines were based on Outern Membrane Vesicles (OMV). One of them is the 4C-MenB (Bexsero). The antigens included in this vaccine’s formulation are, in addition to the OMV from New Zeland epidemic strain 98/254, three recombinant proteins: NadA, NHBA and fHbp. While the role of these recombinant components was deeply characterized, the vesicular contribution in 4C-MenB elicited protection is mediated mainly by porin A and other unidentified antigens. To unravel the relative contribution of these different antigens in eliciting protective antibody responses, we isolated human monoclonal antibodies (mAbs) from single-cell sorted plasmablasts of 3 adult vaccinees peripheral blood. mAbs have been screened for binding to 4C-MenB components by Luminex bead-based assay. OMV-specific mAbs were purified and tested for functionality by serum bactericidal assay (SBA) on 18 different MenB strains and characterized in a protein microarray containing a panel of prioritized meningococcal proteins. The bactericidal mAbs identified to recognize the outer membrane proteins PorA and PorB, stating the importance of PorB in cross-strain protection. In addition, RmpM, BamE, Hyp1065 and ComL were found as immunogenic components of the 4C-MenB vaccine.

Tipologia del documento
Tesi di dottorato
Vezzani, Giacomo
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
Neisseria meningitidis, mAbs
Data di discussione
4 Luglio 2022

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