Long-term persistence of RBD+ memory B cells encoding neutralizing antibodies in SARS-CoV-2 infection

• Published in: Cell reports. Medicine 2021-04, Vol.2 (4), p.100228-100228, Article 100228
• Main Authors: Abayasingam, Arunasingam, Balachandran, Harikrishnan, Agapiou, David, Hammoud, Mohamed, Rodrigo, Chaturaka, Keoshkerian, Elizabeth, Li, Hui, Brasher, Nicholas A., Christ, Daniel, Rouet, Romain, Burnet, Deborah, Grubor-Bauk, Branka, Rawlinson, William, Turville, Stuart, Aggarwal, Anupriya, Stella, Alberto Ospina, Fichter, Christina, Brilot, Fabienne, Mina, Michael, Post, Jeffrey J., Hudson, Bernard, Gilroy, Nicky, Dwyer, Dominic, Sasson, Sarah C., Tea, Fiona, Pilli, Deepti, Kelleher, Anthony, Tedla, Nicodemus, Lloyd, Andrew R., Martinello, Marianne, Bull, Rowena A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Asymptomatic Diseases; COSIN; COVID; COVID-19 - immunology; COVID-19 - pathology; COVID-19 - virology; Female; functional MBCs; Humans; Limit of Detection; longitudinal tracking; Male; memory B cells; Memory B Cells - metabolism; Middle Aged; Neutralization Tests; neutralizing antibodies; Protein Domains - immunology; RBD; RBD tetramer; SARS-CoV-2; SARS-CoV-2 - isolation & purification; SARS-CoV-2 - metabolism; SARS-CoV-2 pseudovirus; Severity of Illness Index; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Time Factors; Young Adult
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2021.100228

Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence of antibody titers declining rapidly after infection and reports of reinfection. Here, we monitor the antibody responses against SARS-CoV-2 receptor-binding domain (RBD) for up to 6 months after infection. While antibody titers are maintained, ∼13% of the cohort’s neutralizing responses return to background. However, encouragingly, in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralizing capacity from these memory B cells. Overall, our study suggests that the loss of neutralizing antibodies in plasma may be countered by the maintenance of neutralizing capacity in the memory B cell repertoire. [Display omitted] Decay of antibody binding to RBD and spike antigen after 6 months11 of 81 (13.6%) participants revert to background neutralizing levelsDespite declining antibody titers, robust memory B cell populations are observedMemory B cells retain potent neutralizing capacity Abayasingam et al. report that despite the declining anti-RBD antibody titers and neutralizing capacity of antibodies in the serum at 6 months, the memory B cells still contain RBD-specific reactivity that have the capacity to generate antibodies that can neutralize SARS-CoV-2 in vitro.