151. Adjuvanted SARS-CoV-2 spike protein vaccination elicits long-lived plasma cells in nonhuman primates.
- Author
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Prabhakaran, Madhu, Matassoli, Flavio, Leggat, David, Hoover, Abigayle, Srikanth, Abhinaya, Wu, Weiwei, Henry, Amy R., Wang, Jennifer, Lin, Bob C., Teng, I-Ting, Schramm, Chaim A., Castro, Mike, Serebryannyy, Leonid, Jean-Baptiste, Nazaire, Moore, Christopher, Gajjala, Suprabhath, Todd, John-Paul M., McCarthy, Elizabeth, Narpala, Sandeep, and Francica, Joseph
- Subjects
SARS-CoV-2 ,PLASMA cells ,IMMUNOLOGIC memory ,T cell receptors ,BONE marrow ,TALL-1 (Protein) ,ANTIBODY formation ,PLASMA cell diseases - 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. Editor's summary: Although much is known about the antibody response to SARS-CoV-2 vaccination, relatively little is known about the elusive cells that make the antibodies. These long-lived plasma cells (LLPCs) reside in bone marrow and, as a consequence, are challenging to study in humans. To better understand these cells in a related species, Prabhakaran et al. longitudinally characterized bone marrow LLPCs in a cohort of nonhuman primates immunized with an adjuvanted spike protein vaccine. Using an antigen-specific LLPC isolation technique, the authors purified spike protein– and receptor binding domain–specific LLPCs from the bone marrow of the animals and determined that their antibody repertoires matched those of memory B cells in the peripheral blood. They also observed that antibodies generated by these LLPCs had undergone somatic hypermutation, which was associated with improved neutralizing and binding capabilities at later time points. Together, these results report a technique to reliably isolate antigen-specific LLPCs and further demonstrate that LLPCs are generated by a SARS-CoV-2 protein vaccine. —Courtney Malo [ABSTRACT FROM AUTHOR]
- Published
- 2024
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