Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Vaccination , COVID-19 SerotherapyABSTRACT
Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , B-Lymphocytes/immunology , COVID-19 , Convalescence , 3T3 Cells , Animals , Antibodies, Monoclonal/isolation & purification , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/isolation & purification , B-Lymphocytes/cytology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/therapy , Chlorocebus aethiops , Disease Models, Animal , Female , HEK293 Cells , Humans , Immunoglobulin Fc Fragments/immunology , Male , Mice , Spike Glycoprotein, Coronavirus/immunology , Vero CellsABSTRACT
Life expectancy has grown tremendously. This incredible achievement for mankind has been obtained mostly thanks to three pillars: hygiene, antibiotics and vaccines. They represent one of the most effective forms of medical intervention. From Jenner's work to new vaccines, immunization has reduced the consequences of infectious diseases. In the last years antimicrobial resistance (AMR) as well as emerging infectious diseases have been rated as major threats for our society, as their toll is forecasted to drastically impinge on human health and economies. Indeed, recently, the whole world has experienced such problems because of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of Covid-19. Herein, we propose an excursus through the three main pillars (hygiene, antibiotics and vaccination) that contributed to improving life expectancy, their clinical and economic impact and the role of vaccines to fight AMR-related diseases and emerging infectious diseases like Covid-19.