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

Cell Rep Med. 2021 Apr 20;2(4):100228. doi: 10.1016/j.xcrm.2021.100228. Epub 2021 Mar 14.


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.

Keywords: COSIN; COVID; RBD; RBD tetramer; SARS-CoV-2; SARS-CoV-2 pseudovirus; functional MBCs; longitudinal tracking; memory B cells; neutralizing antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / immunology
  • Asymptomatic Diseases
  • COVID-19 / immunology
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Female
  • Humans
  • Limit of Detection
  • Male
  • Memory B Cells / metabolism*
  • Middle Aged
  • Neutralization Tests
  • Protein Domains / immunology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Time Factors
  • Young Adult


  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2