학술논문
The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination.
Document Type
Author
Lee F; Emory University.; Nguyen D; Emory University.; Hentenaar I; Emory University.; Morrison-Porter A; Emory.; Solano D; Emory University.; Haddad N; MicroB-plex.; Castrillon C; Emory University.; Lamothe P; Emory University.; Andrews J; Emory University.; Roberts D; Emory University.; Lonial S; Emory University.; Sanz I; Emory University.
Source
Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma cells can be found in the BM. To better understand this paradox, we enrolled 19 healthy adults at 1.5-33 months after SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus-, or SARS-CoV-2-specific antibody secreting cells (ASC) in LLPC (CD19 - ) and non-LLPC (CD19 + ) subsets within the BM. All individuals had IgG ASC specific for influenza, tetanus, and SARS-CoV-2 in at least one BM ASC compartment. However, only influenza- and tetanus-specific ASC were readily detected in the LLPC whereas SARS-CoV-2 specificities were mostly excluded. The ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.61, 0.44, and 29.07, respectively. Even in five patients with known PCR-proven history of infection and vaccination, SARS-CoV-2-specific ASC were mostly excluded from the LLPC. These specificities were further validated by using multiplex bead binding assays of secreted antibodies in the supernatants of cultured ASC. Similarly, the IgG ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.66, 0.44, and 23.26, respectively. In all, our studies demonstrate that rapid waning of serum antibodies is accounted for by the inability of mRNA vaccines to induce BM LLPC.
Competing Interests: Conflict of interest FEL is the founder of Micro-Bplex, Inc., serves on the scientific board of Be Biopharma, is a recipient of grants from the BMGF and Genentech, Inc., and has served as a consultant for Astra Zeneca. IS has consulted for GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol Myer Squibb, and Visterra. FEL, DN, and IS are inventors of the patents concerning the plasma cell survival media related to this work (issued 9/21/21, US 11,124766 B2 PCT/US2016/036650; and issued 9/21/21, US 11,125757 B2). The other authors declare no conflicts of interest.
Competing Interests: Conflict of interest FEL is the founder of Micro-Bplex, Inc., serves on the scientific board of Be Biopharma, is a recipient of grants from the BMGF and Genentech, Inc., and has served as a consultant for Astra Zeneca. IS has consulted for GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol Myer Squibb, and Visterra. FEL, DN, and IS are inventors of the patents concerning the plasma cell survival media related to this work (issued 9/21/21, US 11,124766 B2 PCT/US2016/036650; and issued 9/21/21, US 11,125757 B2). The other authors declare no conflicts of interest.