Human monoclonal antibodies reveal subdominant gonococcal and meningococcal cross-protective antigens
Author:
Troisi MarcoORCID, Fabbrini MonicaORCID, Stazzoni SamueleORCID, Viviani ViolaORCID, Carboni Filippo, Abbiento ValentinaORCID, Fontana Lucia EleonoraORCID, Tomei SaraORCID, Audagnotto MartinaORCID, Santini Laura, Spagnuolo Angela, Antonelli GiadaORCID, Paciello IdaORCID, Vacca Fabiola, Cardamone DarioORCID, Marini EleonoraORCID, Mokhtary PardisORCID, Finetti FrancescaORCID, Giusti FabiolaORCID, Bodini MargheritaORCID, Torricelli GiuliaORCID, Limongi ChiaraORCID, Del Vecchio Mariangela, Favaron Sara, Tavarini Simona, Sammicheli Chiara, Rossi Alessandro, Mandelli Andrea PaolaORCID, Fortini Pietro, Caffarelli CarlaORCID, Gonnelli StefanoORCID, Nuti Ranuccio, Baldari Cosima T.ORCID, Sala Claudia, Tagliabue Aldo, Savino Silvana, Brunelli Brunella, Norais Nathalie, Frigimelica Elisabetta, Bardelli Monia, Pizza MariagraziaORCID, Margarit Immaculada, Delany Isabel, Finco OrettaORCID, Andreano EmanueleORCID, Rappuoli RinoORCID
Abstract
ABSTRACTGonococcus (Gc), a bacterium resistant to most antibiotics causing more than 80 million cases of gonorrhea annually, is a WHO high priority pathogen. Recently, vaccine development prospects were boosted by reports that licensed meningococcus serogroup B (MenB) vaccines provided partial protection against Gc infection. To determine antigens responsible for cross-protection, memory B cells from 4CMenB vaccinated volunteers were single-cell sorted to identify antibodies that kill Gc in a bactericidal assay. Nine different antibodies, all deriving from the IGHV4-34 germline carrying unusually long HCDR3s, recognized the PorB protein, four recognized the lipooligosaccharide (LOS), and four unknown antigens. One of the PorB antibodies, tested in vivo, provided protection from Gc infection. The identification of PorB and LOS as key antigens of gonococcal and meningococcal immunity provides a mechanistic explanation of the cross-protection observed in the clinic and shows that isolating human monoclonal antibodies from vaccinees can be instrumental for bacterial antigen discovery.
Publisher
Cold Spring Harbor Laboratory
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