Periodic Reporting for period 2 - vAMRes (Vaccines as a remedy for antimicrobial resistant bacterial infections)
Periodo di rendicontazione: 2020-05-01 al 2021-10-31
In this context, the ERC Advanced Grant vAMRes focuses on the discovery of monoclonal antibodies (mAbs) against anti-microbial resistant bacteria (Neisseria gonorrhoeae and Escherichia coli) and against the SARS-CoV-2 virus for therapy and for supporting rational vaccine design. During the reporting period, research activities have been conducted on mAbs against N. gonorrhoeae and against SARS-CoV-2.
SARS-CoV-2: By single cell sorting 4,277 SARS-CoV-2 spike protein specific MBCs from 14 Covid-19 survivors, 453 neutralizing antibodies were identified. Only 1.4% of them neutralized the authentic virus in vitro with a potency of 1-10 ng/mL. The most potent neutralizing antibodies recognized the Receptor Binding Domain (RBD), followed by antibodies that recognize the S1 domain, the S-protein trimer and the S2 subunit. The three most potent mAbs, engineered to reduce the risk of antibody dependent enhancement of disease (ADE), prolong half-life and increase tissue distribution, neutralized the authentic virus with less than 10 ng/mL and protected hamsters from viral challenge at a concentration as low as 0.25 mg/Kg (Andreano et al., 2021). Importantly, the most potent mAb (named MAD0004J08) was shown to be active against the so-called Alpha, Beta, Gamma and Delta variants of SARS-CoV-2. MAD0004J08 has been produced on the large scale by an Italian pharmaceutical company and is now in clinical trials. Phase I was recently successfully completed and phase II has started with the administration of the candidate mAb to infected patients by intramuscular injection.
Within the N. gonorrhoeae project, most of the progress has been made in the development of confocal microscopy-based assays, which will soon replace conventional, low-throughput assays, thus bringing microbiology into the 21st century. Data generated so far will be further consolidated and enriched by in vivo experiments which will validate mAb potency in infection settings.