Participants were enrolled and allocated to single blood draws or longitudinal follow-up based on the epidemiology of the contamination and participants availability

Participants were enrolled and allocated to single blood draws or longitudinal follow-up based on the epidemiology of the contamination and participants availability. == Method Details == == Isolation of peripheral blood mononuclear cells (PBMCs), plasma and total IgG from whole blood == Blood draw collection was performed using EDTA tubes and/or syringes pre-filled with heparin. a protective immune response upon vaccination. Keywords:SARS-CoV-2, 2019-nCoV, COVID-19, neutralizing antibody, monoclonal antibody, single B cell analysis == Graphical Abstract == == Highlights == Isolation of highly potent SARS-CoV-2-neutralizing antibodies Longitudinal sampling reveals early class-switched neutralizing response SARS-CoV-2 S-protein-reactive antibodies show little somatic mutation over time Potential antibody precursor sequences identified in SARS-CoV-2-naive individuals In a longitudinal analysis of ICA SARS-CoV-2-infected people, Kreer et al. find highly potent neutralizing antibodies that use a broad spectrum of variable (V) genes and show low levels of somatic mutations. They also identify potential precursor sequences of these SARS-CoV-2-neutralizing antibodies from virus-naive individuals, sampled before the COVID-19 pandemic. This could indicate that neutralizing antibodies can be readily generated from existing germline antibody sequences found in the general populace. == Introduction == By June 2020, over 8.4 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and over 450,000 casualties of the associated coronavirus disease 2019 (COVID-19) were reported (Dong et al., 2020;Huang et ICA al., 2020;Zhou et al., 2020;Zhu et al., 2020). The exponential spread of the computer virus has caused countries to shut down public life with unprecedented interpersonal and economic consequences. Therefore, decoding SARS-CoV-2 immunity to promote development of vaccines as well as potent antiviral drugs is an urgent health need (Sanders et al., 2020). Monoclonal antibodies (mAbs) targeting viral surface proteins have ICA been demonstrated to effectively neutralize viruses such as Ebola computer virus (EBOV) (Ehrhardt et al., 2019;Flyak et al., 2016;Saphire et al., 2018), respiratory syncytial computer virus (RSV) (Kwakkenbos et al., 2010), influenza computer virus (Corti et al., 2011;Joyce et al., 2016;Kallewaard et al., 2016), or human immunodeficiency computer virus 1 (HIV-1) (Walker et al., 2009;Huang et al., 2016a,2016b;Scheid et al., 2011;Schommers et al., 2020;Wu et al., 2010). The most prominent target for an antibody-mediated response on the surface of SARS-CoV-2 virions is the homotrimeric spike (S) protein. The S protein promotes cell entry through conversation of its receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) (Hoffmann et al., 2020;Walls et al., 2020). Antibodies that target the S protein are therefore of particular interest to combat the current pandemic (Burton and Walker, 2020;Sempowski et al., 2020). SARS-CoV-2 contamination induces a humoral immune response of varying magnitude ICA (Duan et al., 2020;Ni et al., 2020), and antibody levels depend on several factors, including disease severity (Long et al., 2020a;Wang et al., Rabbit Polyclonal to RHO 2020b). SARS-CoV-2-reactive as well as SARS-CoV-2-neutralizing antibodies have now been isolated from COVID-19 survivors (Brouwer et al., 2020;Cao et al., 2020;Hansen et al., 2020;Ju et al., 2020;Liu et al., 2020a;Robbiani et al., 2020;Seydoux et al., 2020;Shi et al., 2020;Wu et al., 2020;Zost et al., 2020), immunized animals (Hansen et al., 2020;Wang et al., 2020a;Wrapp et al., 2020a), and phage display libraries (Li et al., 2020;Liu et al., 2020b;Yuan, 2020;Zeng et al., 2020). Such antibodies are of great value to elucidate neutralization mechanisms, inform vaccination strategies, and potentially treat and prevent SARS-CoV-2 contamination, as exhibited in animal models (Cao et al., 2020;Rogers et al., 2020;Zost et al., 2020). The antibodies described target various sites around the S protein, including the RBD (Brouwer et al., 2020;Liu et al., 2020a;Seydoux et al., 2020). However, the affinities and neutralization activities of the reported antibodies vary strongly, and the potential for SARS-CoV-2 escape mutations highlights the need to carefully develop antibody-mediated strategies (Baum et al., 2020). Moreover, little is known about the likelihood of generating such neutralizing antibodies and how they evolve over time, which will be crucial for ICA the development of a broadly active SARS-CoV-2 vaccine. Here, we isolated and sequenced 4,313 S-protein-reactive memory B cells from 12 SARS-CoV-2-infected individuals as early as 8 days after diagnosis (16 days after onset of symptoms). Five patients were followed over a period of 869 days after diagnosis to investigate the dynamics of antibody development against SARS-CoV-2. Besides presenting 28 neutralizing antibodies that are currently being evaluated for clinical application, we provide evidence that antibodies develop early after SARS-CoV-2 contamination with limited ongoing somatic hypermutation. Finally, we identified potential precursor sequences of potent SARS-CoV-2-neutralizing antibodies in naive B cell repertoires from healthy individuals who were sampled before the SARS-CoV-2 pandemic. == Results == == SARS-CoV-2-infected individuals develop a polyclonal memory B cell response against the S protein == To investigate the antibody response.