Madhu Prabhakaran, Flavio Matassoli, David Leggat, Abigayle Hoover, Abhinaya Srikanth, Weiwei Wu, Amy R. Henry, Jennifer Wang, Bob C. Lin, I-Ting Teng, Chaim A. Schramm, Mike Castro, Leonid Serebryannyy, Nazaire Jean-Baptiste, Christopher Moore, Suprabhath Gajjala, John-Paul M. Todd, Elizabeth McCarthy, Sandeep Narpala, Joseph Francica, VRC Production Program, Kizzmekia S. Corbett-Helaire, Daniel C. Douek, Peter D. Kwong, Robert A. Seder, Sarah F. Andrews, Adrian B. McDermott

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

  • General Medicine
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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.

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