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

D Fooksman(Albert Einstein College of Medicine)|📗📗📗📗◻️•D Schaefer-Babajew(Rockefeller University)|📒📒📒◻️◻️•J Wilmore(Upstate Medical University)|📒📒📒◻️◻️• M Sajadi & P Habibzadeh & G Lewis(University of Maryland)|📘📘📘📘📘• S Bjarnarson (University of Iceland)|📘📘📘📘📘

Published onApr 13, 2024
Reviews of "The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination"
key-enterThis Pub is a Review of
The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination
The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination
Description

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.

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Summary of Reviews: The preprint investigates the longevity of plasma cells induced by SARS-CoV-2 mRNA vaccines compared to those induced by tetanus and influenza vaccines. Despite the presence of SARS-CoV-2-specific plasma cells in the bone marrow, they are mostly excluded from the long-lived plasma cell (LLPC) compartment, potentially explaining the short-lived serologic response observed after vaccination. This suggests that the rapid waning of serum antibodies following SARS-CoV-2 vaccination may be attributed to the inability of mRNA vaccines to induce LLPC in the bone marrow. However, reviewers suggest caution in interpreting the data, particularly regarding the classification of long-lived plasma cells as well as the researchers' definitive conclusions due to methodological limitations (heavy reliance on flow cytometry-based classification of plasma cell subsets) and sample heterogeneity.

Reviewer 1 (David F…) | 📗📗📗📗◻️

Reviewer 2 (Dennis S…) | 📒📒📒 ◻️◻️

Reviewer 3 (Joel W…) | 📒📒📒 ◻️◻️

Reviewer 4 (Mohammad S… & Parham H… & George L…) | 📘📘📘📘📘

Reviewer 5 (Stefania B…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

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