The BNT162b2 mRNA Vaccine Against SARS-CoV-2 Reprograms Both Adaptive and Innate Immune Responses

Föhse, F. Konstantin; Geckin, Büsra; Overheul, Gijs J.; Maat, Josephine van de; Kılıç, Gizem; Bulut, Özlem; Dijkstra, Helga; Lemmers, Heidi; Sarlea, S. Andrei; Reijnders, Maartje; Hoogerwerf, Jacobien J.; Oever, Jaap ten; Simonetti, Elles; Veerdonk, Frank L. van de; Joosten, Leo A. B.; Haagmans, Bart L.; Crevel, Reinout van; Li, Yang; Rij, Ronald P. van; Kessel, C. Geurtsvan; Jonge, Marien I. de; Domínguez‐Andrés, Jorge; Netea, Mihai G.

doi:10.2139/ssrn.3839624

Cited by 21 publications

(29 citation statements)

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“…The effects of the mRNA-LNP platform reported here on the innate immune responses is in line with recently published human data generated three weeks after the first shot, in which PBMCs isolated from individuals vaccinated with one dose of the anti-COVID-19 Pfizer-BioNTech mRNA vaccine responded with significantly higher production of TNFα and IL-1β after stimulation with Candida albicans compared with the response before vaccination (Föhse et al, 2021). However, stimulation of cells with other stimuli such as influenza and different TLR ligands showed no significant difference before and after 1 st vaccination, and these effects seem to be lost after subsequent doses (Föhse et al, 2021). If the potential innate immune fitness benefits from the first exposure to mRNA-LNPs reported here for mice and supported by human in vitro restimulation data might be dampened by the subsequent shots, then we would expect that people exposed to multiple mRNA-LNP shots ultimately become more vulnerable to infections.…”

Section: Discussionsupporting

confidence: 88%

“…The possible short and long-term immunological changes of the mRNA-LNP vaccine outside the induction of antigen-specific anti-SARS-CoV-2 responses are unknown. A recent human study awaiting peer-review reported innate and adaptive immune reprogramming with this platform (Föhse et al, 2021), while single-cell RNA-seq studies on human white blood cells derived from vaccinated people also revealed significant changes in innate immune cells (Arunachalam et al, 2021). Whether the reported changes are long-lasting and can influence immune fitness or interfere with the responses induced by other vaccines remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

“…The possible short and long-term immunological changes of the mRNA-LNP vaccine outside the induction of antigenspecific anti-SARS-CoV-2 responses are unknown. A recent human study awaiting peer-review reported innate and adaptive immune reprogramming with this platform (Föhse et al, 2021), while single-cell RNA-seq studies on human white blood cells derived from vaccinated people also revealed significant changes in innate immune weeks post-inoculation, the anti-HA responses were determined in the serum using ELISA and the GC B cell responses in the skin draining lymph nodes monitored by flow cytometry (Supplemental Figure 1), as we previously described (Ndeupen et al, 2022). We found that pre-exposure to mRNA coding for an irrelevant protein (eGFP) or empty LNPs significantly decreased the anti-HA responses, both on antibody and GC B cell levels (Figure 1B and C).…”

Section: Introductionmentioning

confidence: 99%

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Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Qin

Igyártó

2022

Preprint

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Billions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. Here we bring experimental evidence that pre-exposure to mRNA-LNPs or its LNP component has effects on both innate and adaptive immune responses. Pre-exposure to mRNA-LNPs led to long-term, platform-specific inhibition of the adaptive immune responses. As such, mice responded with lower antibody responses when exposed the second time to the mRNA-LNP platform, but with undisturbed adaptive immune responses to protein-based Alum or AddaVax-adjuvanted vaccines. On the other hand, we report that after pre-exposure to mRNA-LNPs, resistance of mice to heterologous infections with influenza virus and Candida albicans is likely enhanced. Interestingly, mice pre-exposed to mRNA-LNPs can pass down the acquired immune traits to their offspring, providing better protection. In summary, the mRNA-LNP vaccine platform induces long-term immunological changes that can affect both humoral responses and heterologous protection against infections. More studies are needed to understand in-depth the mechanisms responsible for these effects.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Qin

Igyártó

2022

Preprint

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“…Possible short and long-term effects on cell metabolism from spike S protein produced by COVID-19 vaccination will be discussed. Researchers have warned that COVID-19 mRNA vaccine induces complex reprogramming of innate immune responses and biodistribution that should be considered in the development and use of mRNA-based vaccines [5,6]. It has been reported [6] that intramuscular vaccines in monkeys remain near the site of injection at the arm muscle and local lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

The effect of COVID-19 mRNA vaccine on human lung carcinoma cells in vitro by means of Raman spectroscopy and imaging

Abramczyk

Surmacki

2022

Preprint

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The paper presents the effect of COVID-19 mRNA (Pfizer/BioNTech) vaccine on human lung carcinoma epithelial cells (A549) studied by means of Raman spectroscopy and imaging. The paper will also focus on Raman imaging as a tool to explore apoptosis and oxidative phosphorylation in mitochondrial dysfunctions. The presented Raman results show alterations in the reduction-oxidation pathways associated with cytochrome c. We found that the COVID-19 mRNA vaccine modulates the concentration of cytochrome c upon incubation with tumorous lung cells. Concentration of oxidized form of cytochrome c in mitochondria of lung cells has been shown to decrease upon incubation the mRNA vaccine. Lower concentration of oxidized cytochrome c in mitochondria indicates lower effectiveness of oxidative phosphorylation (respiration), reduced apoptosis and lessened ATP production. Moreover, mRNA vaccine increases significantly de novo lipids synthesis in lipid droplets and alterations in biochemical composition that suggest the increasing role of signaling. mRNA vaccine does not produce statistically significant changes in cell nucleus. The observed alterations in biochemical profiles upon incubation with mRNA vaccine in the specific organelles of the tumorous lung cells are similar to those we observe for other types of cancer, particularly brain glial cells.

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“…Anti-COVID-19 vaccines (BNT162b2) is one of the world's most commonly used. This vaccine is based on a lipid nanoparticle-formulated, nucleoside-modified mRNA that encodes a prefusion stabilized form of the spike (S)-protein generated from the SARS-CoV-2 strain (Föhse et al, 2021). BNT162b2 delivers the precise genetic information of the immunogen to antigen presenting cells and elicits potent cellular and humoral immune responses (Sahin et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comparative study of IL- 2, IL- 6 levels for recovered COVID-19 patients and vaccinated participants

Saleh

Mohammed

Al-badri

2022

ijhs

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SARS-CoV-2 transmission and hospitalization can be reduced primarily by vaccination. BNT162b2-mRNA vaccine induced both humoral and cellular immune responses against spike proteins. The aim of this cross-sectional study conducted in Wasit Governorate/Iraq is to compare IL-2 and IL-6 levels for recovered COVID-19 patients and participants who were vaccinated with BNT162b2 mRNA vaccine, we used systems serology to investigate the effects and benefit of the BNT162b2 mRNA COVID-19 vaccine on the level of the immune response. A total of 160 male and female blood specimens were collected from the various hospitals and vaccination centers throughout the governorate and divided into four groups: 40 healthy control participants, 40 symptomatic recovered COVID-19 patients (after 1-3 months), 40 participants vaccinated with the 1st dose of BNT162b2 mRNA (after 21 days of 1st dose), and 40 participants vaccinated with the 2nd dose of BNT162b2 mRNA (after 20-30 days of 2nd dose), aged between (18-61) years old, serum cytokines levels were assayed by ELISA method. By comparing the levels of IL-2 and IL-6 in all our studied groups, our findings found that the groups vaccinated with two doses of BNT162b2 mRNA vaccines was recorded the highest response level compared to the symptomatic recovered COVID-19 group.

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The BNT162b2 mRNA Vaccine Against SARS-CoV-2 Reprograms Both Adaptive and Innate Immune Responses

Cited by 21 publications

References 0 publications

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

The effect of COVID-19 mRNA vaccine on human lung carcinoma cells in vitro by means of Raman spectroscopy and imaging

Comparative study of IL- 2, IL- 6 levels for recovered COVID-19 patients and vaccinated participants

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