Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals

By D. Robbiani, C. Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, A. Cho, Marianna Agudelo, C. Barnes, A. Gazumyan, Shlomo Finkin and 36 more. 2020

1,837 citations recorded by the source corpus.

During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC50 values) as low as 2 ng ml−1. In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective. Although rare, antibodies against the receptor-binding domain of SARS-CoV-2 that showed potent antiviral activity were obtained from all tested convalescent individuals, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Subfields: Infectious Diseases

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In Infectious Diseases

1. Kwok-Yung Yuen
2. D. Veesler
3. A. Walls
4. M. A. Tortorici
5. K. To
6. A. Aschenbrenner
7. V. Cheng
8. Kwok-Hung Chan

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “These findings showed that the RBD is a prime target of neutralizing Abs upon natural CoV infection, in agreement with reports of the isolation of RBD-targeted neutralizing Abs from COVID-19 convalescent patients (Barnes et al., 2020; Brouwer et al., 2020; Robbiani et al., 2020; Seydoux et al., 2020”
• COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing (2020, background): “Although neutralizing antibody develops rapidly after infection [5,6], recent studies showed that antibody titers start to decline as early as 1-2 months after the acute infection [7,8].”
• Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial (2020, methodology): “17,18 Antibodies capable of neutralising live SARS-CoV-2 were induced by day 28 with titres of 51 (PHE MNA 80 ) and 218 (PHE PRNT 50 ), and with titres of 29 (Marburg VN) or 136 (PHE MNA 80 ) after a booster dose, as measured using different assays.”
• Evolution of antibody immunity to SARS-CoV-2 (2021, background): “3 nature research | reporting sum m ary April 2020 Eukaryotic cell lines Policy information about cell lines Cell line source(s) 293T (ATCC CRL-11268) 293TAce2 (derived from 293T) Robbiani, 2020 Authentication Not authenticated after purchase from ATCC.”
• Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “…have documented the development of IgG, IgA, and IgM against S and N within 2 weeks after onset of symptoms in SARS-CoV-2-infected individuals and analyzed the kinetics in the early convalescent phase (Long et al., 2020; Luchsinger et al., 2020; Pre´vost et al., 2020; Robbiani et al., 2020).”
• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, positive): “Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a major threat to global public health, many studies have focused efforts on discovery of potent neutralizingmonoclonal antibodies (mAbs) against the spike (S) protein of SARS-CoV-2 (Baum et al., 2020a; Cao et al.”