SARS-CoV-2 mRNA vaccines induce a robust germinal centre reaction in humans

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA)-based vaccines are ~95% effective in preventing coronavirus disease 2019. However, the dynamics of antibody secreting plasmablasts (PBs) and germinal centre (GC) B cells induced by these vaccines in SARS-CoV-2 naïve and antigen-experienced humans remains unclear. Here we examined peripheral blood and/or lymph node (LN) antigen-specific B cell responses in 32 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding the full-length SARS-CoV-2 spike (S) gene. Circulating IgG- and IgA-secreting PBs targeting the S protein peaked one week after the second immunization then declined and were undetectable three weeks later. PB responses coincided with maximal levels of serum anti-S binding and neutralizing antibodies to a historical strain as well as emerging variants, especially in individuals previously infected with SARS-CoV-2, who produced the most robust serological responses. Fine needle aspirates of draining axillary LNs identified GC B cells that bind S protein in all participants sampled after primary immunization. GC responses increased after boosting and were detectable in two distinct LNs in several participants. Remarkably, high frequencies of S-binding GC B cells and PBs were maintained in draining LNs for up to seven weeks after first immunization, with a substantial fraction of the PB pool class-switched to IgA. GC B cell-derived monoclonal antibodies predominantly targeted the RBD, with fewer clones binding to the N-terminal domain or shared epitopes within the S proteins of human betacoronaviruses OC43 and HKU1. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a robust and persistent GC B cell response that engages pre-existing as well as new B cell clones, which enables generation of high-affinity, broad, and durable humoral immunity.

Correlation Between BNT162b2 mRNA Covid-19 Vaccine-associated Hypermetabolic Lymphadenopathy and Humoral Immunity in Patients With Hematologic Malignancy

“…The immune responses elicited by vaccines [31] is studied in depth lately, particularly since the introduction of the novel anti-SARS-CoV-2 mRNA vaccines [32][33][34]. After intramuscular administration of the vaccine, antigen-presenting cells (APCs) loaded with antigen migrate to regional lymph nodes, where they present peptide antigens and elicit two main responses: cellular response, with the formation of cytotoxic T lymphocytes capable of directly killing infected cells, and humoral response, which depends on B-cells proliferation in the germinal center (GC) of the lymph node and the formation of matured Bcells as antibody secreting plasma cells and memory B-cells [32].…”

A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

“…( A and B ) ELISA binding to recombinant RBD from (A) and neutralizing activity in Vero-TMPRSS2 cells against (B) indicated SARS-CoV-2 strains by the indicated mAbs. ELISA binding to D614G RBD previously reported in ( 29 ). Baseline for area under the curve was set to the mean + three times the standard deviation of background binding to bovine serum albumin.…”

“…GC B cells were analyzed in aspirates from the draining axillary lymph nodes of 12 participants after vaccination. We verified the specificity of the GC response by generating a panel of recombinant human mAbs from single cell-sorted S + GC B cells isolated from three participants ( 29 ). The majority of these vaccine-induced antibodies are directed against the RBD.…”

“…From a pool of S + GC B cell-derived mAbs, we selected 13 human anti-RBD mAbs that bound avidly to the predominantly circulating WA1/2020 D614G SARS-CoV-2 strain referred to hereafter as the D614G strain ( 29 , 30 ). We assessed mAbs binding to recombinant RBDs derived from the D614G strain and three SARS-CoV-2 variants, B.1.1.7, B.1.351 and B.1.1.248 by enzyme-linked immunosorbent assay (ELISA).…”

“…The source cells are predominantly plasmablasts or memory B cells that are isolated from blood after infection or vaccination ( 37 ). Here, we describe 2C08, a SARS-CoV-2 vaccine-induced mAb cloned from a GC B cell clone isolated from a draining axillary lymph node sampled from a healthy adult after receiving their second dose of mRNA-based vaccine ( 29 ). 2C08 is a potently neutralizing antibody that targets the receptor binding motif within the RBD of SARS-CoV-2 S protein and blocks infection by circulating SARS-CoV-2 and emerging variants of concern both in vitro and in vivo .…”