mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection

Ivanova, Ellie N.; Shwetar, Jasmine; Devlin, Joseph C.; Buus, Terkild B.; Gray-Gaillard, Sophie; Koide, Akiko; Cornelius, Amber; Samanovic, Marie I.; Herrera, Alberto; Mimitou, Eleni P.; Zhang, Chenzhen; Karmacharya, Trishala; Desvignes, Ludovic; Ødum, Niels; Smibert, Peter; Ulrich, Robert J.; Mulligan, Mark J.; Koide, Shohei; Ruggles, Kelly V.; Herati, Ramin S.; Koralov, Sergei B.

doi:10.1016/j.isci.2023.108572

“…Interestingly, the Ad vectors persist for weeks, yet specific humoral immunity is also short-lasting 3,4 . Furthermore, recent evidence showed that the mRNA vaccine platforms do not induce strong type I IFN responses 43 . In vitro and animal studies suggest that type I IFN may play a role in LLPC 44,45 , but whether it is important for the generation of in vivo human LLPC will need further studies.…”

Section: Discussionmentioning

confidence: 99%

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

Nguyen,

Hentenaar,

Morrison-Porter

et al. 2024

Preprint

1

0

View full text Add to dashboard Cite

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.

show abstract

“…Interestingly, the Ad vectors persist for weeks, yet speci c humoral immunity is also short-lasting 3,4 . Furthermore, recent evidence showed that the mRNA vaccine platforms do not induce strong type I IFN responses 43 . In vitro and animal studies suggest that type I IFN may play a role in LLPC 44,45 , but whether it is important for the generation of in vivo human LLPC will need further studies.…”

Section: Discussionmentioning

confidence: 99%

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

Lee,

Nguyen,

Hentenaar

et al. 2024

Preprint

0

View full text Add to dashboard Cite

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.

show abstract

Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

Rubio-Casillas,

Cowley,

Raszek

et al. 2024

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection

Cited by 8 publications

References 88 publications

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

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

Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

Contact Info

Product

Resources

About