Isolation and characterization of highly functional human monoclonal antibodies against Neisseria gonorrhoeae and SARS-CoV-2

BACKGROUND Monoclonal antibodies (mAbs) are becoming increasingly popular in the infectious disease field where they represent a promising and innovative class of therapeutics. In this context, the aim of this PhD thesis was to identify highly effective mAbs against Neisseria gonorrhoeae (Ng) and SARS-CoV-2. METHODS Peripheral blood mononuclear cells (PBMCs) from Bexsero vaccinees and COVID-19 convalescent patients were collected. mAbs were isolated from memory B cells (MBC) and plasma cells (PCs) and subsequently their binding profile and functionality were analysed. RESULTS From Bexsero vaccinees, 17 mAbs capable of neutralizing Neisseria gonorrhoeae by in vitro bactericidal assay were identified. mAb potency (IC50), established by complement-mediated killing, correlated with the binding profile. Indeed, mAbs targeting well-represented surface structures were the most potent. From COVID-19 patients, 453 neutralizing antibodies were identified. The most powerful antibody recognized the spike protein receptor-binding domain with IC100 lower than 10 ng/mL. CONCLUSIONS High-throughput screening of mAbs allowed the identification of potent molecules capable of killing Neisseria gonorrhoeae and neutralizing SARS-CoV- 2. On one hand, this work contributed to better understand the protection against gonococcal infection. Indeed, results suggest that complement-mediated killing, may be used as correlate of protection and predict vaccine efficacy. On the other, a highly potent mAb against the etiological agent of COVID-19 was identified and well-characterized in vitro and in vivo, where prophylactic and therapeutic efficacy were demonstrated by extraordinarily low amounts of the candidate medication.