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SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA
Doan C Nguyen1, Ian T Hentenaar1, Andrea Morrison-Porter1
1Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective at protecting from severe disease, but the protective antibodies wane rapidly even though SARS-CoV-2-specific plasma cells can be found in the bone marrow (BM). Here, to explore this paradox, we enrolled 19 healthy adults at 2.5-33 months after receipt of a SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus- or SARS-CoV-2-specific antibody-secreting cells (ASCs) in long-lived plasma cell (LLPC) and non-LLPC subsets within the BM. Only influenza- and tetanus-specific ASCs were readily detected in the LLPCs, whereas SARS-CoV-2 specificities were mostly absent. The ratios of non-LLPC:LLPC for influenza, tetanus and SARS-CoV-2 were 0.61, 0.44 and 29.07, respectively. In five patients with known PCR-proven history of recent infection and vaccination, SARS-CoV-2-specific ASCs were mostly absent from the LLPCs. We show similar results with measurement for secreted antibodies from BM ASC culture supernatant. While serum IgG titers specific for influenza and tetanus correlated with IgG LLPCs, serum IgG levels for SARS-CoV-2, which waned within 3-6 months after vaccination, were associated with IgG non-LLPCs. In all, our studies suggest that rapid waning of SARS-CoV-2-specific serum antibodies could be accounted for by the absence of BM LLPCs after these mRNA vaccines.
Insights
SARS-CoV-2 mRNA vaccines induce antibodies, but protective levels wane. This study found a lack of long-lived plasma cells in bone marrow specific to SARS-CoV-2, explaining antibody decline.
Area of Science:
- Immunology
- Vaccinology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective but antibody protection wanes rapidly.
- SARS-CoV-2-specific plasma cells are found in bone marrow (BM), creating a paradox.
Purpose of the Study:
- To investigate the paradox of waning SARS-CoV-2 antibodies despite the presence of plasma cells in bone marrow.
- To compare SARS-CoV-2-specific antibody-secreting cells (ASCs) with those from influenza and tetanus vaccines in healthy adults.
Main Methods:
- Enrolled 19 healthy adults 2.5-33 months post-SARS-CoV-2 mRNA vaccination.
- Measured influenza-, tetanus-, and SARS-CoV-2-specific ASCs in bone marrow long-lived plasma cell (LLPC) and non-LLPC subsets.
- Analyzed secreted antibodies from BM ASC culture supernatant and correlated serum IgG titers with BM LLPCs.
Main Results:
- Influenza- and tetanus-specific ASCs were detected in LLPCs, but SARS-CoV-2 specificities were largely absent.
- The ratio of non-LLPC:LLPC for SARS-CoV-2 was significantly higher (29.07) compared to influenza (0.61) and tetanus (0.44).
- Waning SARS-CoV-2 serum IgG levels correlated with non-LLPCs, unlike influenza and tetanus, which correlated with LLPCs.
Conclusions:
- The rapid waning of SARS-CoV-2-specific serum antibodies after mRNA vaccination may be due to the absence of bone marrow LLPCs.
- Findings suggest a distinct immune memory profile for SARS-CoV-2 compared to established vaccines like influenza and tetanus.
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