Adjuvanted SARS-CoV-2 spike protein vaccination elicits long-lived plasma cells in nonhuman primates

Abstract

Durable humoral immunity is mediated by long-lived plasma cells (LLPCs) that reside in the bone marrow. It remains unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein vaccination is able to elicit and maintain LLPCs. Here, we describe a sensitive method to identify and isolate antigen-specific LLPCs by tethering antibodies secreted by these cells onto the cell surface. Using this method, we found that two doses of adjuvanted SARS-CoV-2 spike protein vaccination are able to induce spike protein–specific LLPC reservoirs enriched for receptor binding domain specificities in the bone marrow of nonhuman primates that are detectable for several months after vaccination. Immunoglobulin gene sequencing confirmed that several of these LLPCs were clones of memory B cells elicited 2 weeks after boost that had undergone further somatic hypermutation. Many of the antibodies secreted by these LLPCs also exhibited improved neutralization and cross-reactivity compared with earlier time points. These findings establish our method as a means to sensitively and reliably detect rare antigen-specific LLPCs and demonstrate that adjuvanted SARS-CoV-2 spike protein vaccination establishes spike protein–specific LLPC reservoirs.

The picture theory of seven pathways associated with COVID-19 in the real world

“…The protease neutrophil elastase (NE) e ciently cleaves SP, exposes amyloidogenic segments, and accumulates the most amyloidogenic synthetic spike peptide, but full-length folded SP does not form amyloid brils 121 122 . SARS-CoV-2 SP vaccination establishes long-lived SP-speci c plasma cell reservoirs in the bone marrow of nonhuman primates 123 . The SP might have induced immune reactions in humans.…”

The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination

“…Early in the pandemic, reports of SARS2 spike-specific IgG ASC were readily identified in the BM after SARS2 infection or vaccination 6,7 , or in the non-human primates after SARS2 spike protein vaccination 8 , suggesting long-lived humoral protection without serologic confirmation. Interestingly, BM ASC compartments are quite heterogeneous comprising of early-minted ASC (new arrivals) of which some progressively mature into LLPC 9–14 .…”

“…Early in the pandemic, reports of SARS2 spike-specific IgG ASC were readily identified in the BM after SARS2 infection or vaccination 6,7 , or in the non-human primates after SARS2 spike protein vaccination 8 , suggesting long-lived humoral protection without serologic confirmation.…”