Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis
Highlights
Coronavirus disease 2019 (COVID-19) mRNA vaccines induce robust immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet their cellular/molecular mode of action and the etiology of the induced adverse events (AEs) remain elusive.
Lipid nanoparticles (LNPs) probably have a broad distribution in human tissues/organs; they may also (along with the packaged mRNA) exert a proinflammatory action.
COVID-19 mRNA vaccines encode a transmembrane SARS-CoV-2 spike (S) protein; however, shedding of the antigen and/or related peptide fragments into the circulation may occur.
Binding of circulating S protein to angiotensin-converting enzyme 2 (ACE2) (that is critical for the renin–angiotensin system balance) or to other targets, along with the possibility of molecular mimicry with human proteins, may contribute to the vaccination-related AEs.
The benefit–risk profile remains in favor of COVID-19 vaccination, yet prospective pharmacovigilance and long-term monitoring of vaccinated recipients should be a public health priority.
Vaccination is a major tool for mitigating the coronavirus disease 2019 (COVID-19) pandemic, and mRNA vaccines are central to the ongoing vaccination campaign that is undoubtedly saving thousands of lives. However, adverse effects (AEs) following vaccination have been noted which may relate to a proinflammatory action of the lipid nanoparticles used or the delivered mRNA (i.e., the vaccine formulation), as well as to the unique nature, expression pattern, binding profile, and proinflammatory effects of the produced antigens – spike (S) protein and/or its subunits/peptide fragments – in human tissues or organs. Current knowledge on this topic originates mostly from cell-based assays or from model organisms; further research on the cellular/molecular basis of the mRNA vaccine-induced AEs will therefore promise safety, maintain trust, and direct health policies.
Keywords
Fighting the COVID-19 pandemic with SARS-CoV-2 S protein-encoding mRNA vaccines
Anti-SARS-CoV-2 mRNA vaccines and their reported adverse effects
In this context, frequent booster immunizations may increase the frequency and/or the severity of the reported AEs.
Vaccine-encoded antigen distribution in the human body and possible interactions with human proteins
The SARS-CoV-2 S protein-induced effects in mammalian cells or model organisms
S protein-induced proinflammatory responses and unique gene expression signatures following vaccination
The need to investigate the molecular basis of vaccination-induced AEs
Concluding remarks
Acknowledgments
The authors received no funding for the preparation of this opinion article.
Author contributions
I.P.T.: conceptualization, writing, and preparation of the figures. E.T., D.P., H.A., M.P., A.S., E.A., E.K. and M.A.D.: review, comments, and further additions. All authors contributed to discussions of the scope of this opinion article and approved the final revised version of the manuscript.
Declarations of interests
The authors declare no competing interests related to this opinion article.
References
- Jin J.
- et al.
Individual and community-level risk for COVID-19 mortality in the United States.
Nat. Med. 2021; 27: 264-269View in Article- O’Driscoll M.
- et al.
Age-specific mortality and immunity patterns of SARS-CoV-2.
Nature. 2021; 590: 140-145View in Article- Gaebler C.
- et al.
Evolution of antibody immunity to SARS-CoV-2.
Nature. 2021; 591: 639-644View in Article- Andersson M.I.
- et al.
SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus.
Wellcome Open Res. 2020; 5: 181View in Article- Wang W.
- et al.
Detection of SARS-CoV-2 in different types of clinical specimens.
JAMA. 2020; 323: 1843-1844View in Article- Wölfel R.
- et al.
Virological assessment of hospitalized patients with COVID-2019.
Nature. 2020; 581: 465-469View in Article- Chen G.
- et al.
Clinical and immunological features of severe and moderate coronavirus disease 2019.
J. Clin. Invest. 2020; 130: 2620-2629View in Article- Deinhardt-Emmer S.
- et al.
Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage.
eLife. 2021; 10e60361View in Article- Fajnzylber J.
- et al.
SARS-CoV-2 viral load is associated with increased disease severity and mortality.
Nat. Commun. 2020; 11: 5493View in Article- Gupta A.
- et al.
Extrapulmonary manifestations of COVID-19.
Nat. Med. 2020; 26: 1017-1032View in Article- Andreakos E.
- et al.
A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection.
Nat. Immunol. 2022; 23: 159-164View in Article- Galani I.-E.
- et al.
Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison.
Nat. Immunol. 2021; 22: 32-40View in Article- Trougakos I.P.
- et al.
Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications.
J. Biomed. Sci. 2021; 28: 9View in Article- Gkogkou E.
- et al.
Expression profiling meta-analysis of ACE2 and TMPRSS2, the putative anti-inflammatory receptor and priming protease of SARS-CoV-2 in human cells, and identification of putative modulators.
Redox Biol. 2020; 36101615View in Article- Muus C.
- et al.
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
Nat. Med. 2021; 27: 546-559View in Article- Ziegler C.G.K.
- et al.
SARS-CoV-2 Receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues.
Cell. 2020; 181: 1016-1035- Blomberg B.
- et al.
Long COVID in a prospective cohort of home-isolated patients.
Nat. Med. 2021; 27: 1607-1613View in Article- MartÃnez-Flores D.
- et al.
SARS-CoV-2 vaccines based on the spike glycoprotein and implications of new viral variants.
Front. Immunol. 2021; 12701501View in Article- Jackson C.B.
- et al.
Mechanisms of SARS-CoV-2 entry into cells.
Nat. Rev. Mol. Cell Biol. 2022; 23: 3-20View in Article- Heinz F.X.
- Stiasny K.
Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action.
NPJ Vaccines. 2021; 6: 104View in Article- European Medicines Agency
Comirnaty Assessment Report COVID-19 Vaccine Comirnaty. EMA/707383/2020 Corr.1*1.
European Medicines Agency, 2021View in Article- European Medicines Agency
Moderna Assessment Report COVID-19 Vaccine Moderna. EMA/15689/2021 Corr.1*1.
European Medicines Agency, 2021View in Article- Moghimi S.M.
Allergic reactions and anaphylaxis to LNP-based COVID-19 vaccines.
Mol. Ther. 2021; 29: 898-900View in Article- Igyártó B.Z.
- et al.
Future considerations for the mRNA–lipid nanoparticle vaccine platform.
Curr. Opin. Virol. 2021; 48: 65-72View in Article- Chaudhary N.
- et al.
mRNA vaccines for infectious diseases: principles, delivery and clinical translation.
Nat. Rev. Drug Discov. 2021; 20: 817-838View in Article- Chung Y.H.
- et al.
COVID-19 vaccine frontrunners and their nanotechnology design.
ACS Nano. 2020; 14: 12522-12537View in Article- Pegu A.
- et al.
Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants.
Science. 2021; 373: 1372-1377View in Article- Sahin U.
- et al.
BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans.
Nature. 2021; 595: 572-577View in Article- Trougakos I.P.
- et al.
Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients.
BMC Med. 2021; 19: 208View in Article- Gagne M.
- et al.
Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung.
Cell. 2022; 185: 113-130- Barda N.
- et al.
Safety of the BNT162b2 mRNA Covid-19 vaccine in a nationwide setting.
N. Engl. J. Med. 2021; 385: 1078-1090View in Article- GarcÃa-Grimshaw M.
- et al.
Neurologic adverse events among 704,003 first-dose recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico: a nationwide descriptive study.
Clin. Immunol. 2021; 229108786View in Article- Klein N.P.
- et al.
Surveillance for adverse events after COVID-19 mRNA vaccination.
JAMA. 2021; 326: 1390-1399View in Article- Patone M.
- et al.
Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.
Nat. Med. 2021; 27: 2144-2153View in Article- Li X.
- et al.
Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study.
BMJ. 2021; 373n1435View in Article- Oster M.E.
- et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US From December 2020 to August 2021.
JAMA. 2022; 327: 331-340View in Article- Montgomery J.
- et al.
Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military.
JAMA Cardiol. 2021; 6: 1202-1206View in Article- Hoeg T.
- et al.
SARS-CoV-2 mRNA vaccination-associated myocarditis in children ages 12–17: a stratified national database analysis.
medRxiv. 2021; (Published online September 8, 2021)View in Article- Li X.
- et al.
Myocarditis following COVID-19 BNT162b2 vaccination among adolescents in Hong Kong.
JAMA Pediatr. 2022; (Published online February 25, 2022)View in Article- Verbeke R.
- et al.
Three decades of messenger RNA vaccine development.
Nanotoday. 2019; 28100766View in Article- Ndeupen S.
- et al.
The mRNA–LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory.
iScience. 2021; 24103479- Parhiz H.
- et al.
Added to pre-existing inflammation, mRNA–lipid nanoparticles induce inflammation exacerbation (IE).
J. Control. Release. 2021; 344: 50-61View in Article- Yang R.
- et al.
A core–shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity.
Signal Transduct. Target Ther. 2021; 6: 213View in Article- Pardi N.
- et al.
Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes.
J. Control. Release. 2015; 217: 345-351View in Article- Hassett K.J.
- et al.
Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines.
Mol. Ther. Nucleic Acids. 2019; 15: 1-11- Ogata A.F.
- et al.
Circulating SARS-CoV-2 vaccine antigen detected in the plasma of mRNA-1273 vaccine recipients.
Clin. Infect. Dis. 2021; 74: 715-718View in Article- Bansal S.
- et al.
Cutting edge: circulating exosomes with COVID spike protein are induced by BNT162b2 (Pfizer-BioNTech) vaccination prior to development of antibodies: a novel mechanism for immune activation by mRNA vaccines.
J. Immunol. 2021; 207: 2405-2410View in Article- Cognetti J.S.
- Miller B.L.
Monitoring serum spike protein with disposable photonic biosensors following SARS-CoV-2 vaccination.
Sensors (Basel). 2021; 21: 5827View in Article- Goel R.R.
- et al.
mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.
Science. 2021; 374abm0829View in Article- Terpos E.
- et al.
Sustained but declining humoral immunity against SARS-CoV-2 at 9 months postvaccination with BNT162b2: a prospective evaluation in 309 healthy individuals.
Hemasphere. 2022; 6e677View in Article- Watanabe Y.
- et al.
Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine.
ACS Cent. Sci. 2021; 7: 594-602View in Article- Li Y.
- et al.
Linear epitope landscape of the SARS-CoV-2 spike protein constructed from 1,051 COVID-19 patients.
Cell Rep. 2021; 34108915View in Article- Hwa K.-Y.
- et al.
Peptide mimicrying between SARS coronavirus spike protein and human proteins reacts with SARS patient serum.
J. Biomed. Biotechnol. 2008; 2008326464View in Article- Kanduc D.
- Shoenfeld Y.
Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine.
Immunol. Res. 2020; 68: 310-313View in Article- O’Donoghue S.I.
- et al.
SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms.
Mol. Syst. Biol. 2021; 17e10079View in Article- Kowarz E.
- et al.
Vaccine-induced COVID-19 mimicry syndrome.
eLife. 2022; 11e74974View in Article- Kreye J.
- et al.
A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model.
Cell. 2020; 183: 1058-1069- Freitas R.S.
- et al.
SARS-CoV-2 spike antagonizes innate antiviral immunity by targeting interferon regulatory factor 3.
Front. Cell. Infect. Microbiol. 2021; 11789462View in Article- Visvabharathy L.
- et al.
Neuro-COVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination.
medRxiv. 2021; (Published online October 29, 2021)View in Article- Murphy W.J.
- Longo D.L.
A possible role for anti-idiotype antibodies in SARS-CoV-2 infection and vaccination.
N. Engl. J. Med. 2022; 386: 394-396View in Article- Zuo Y.
- et al.
Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19.
Sci. Transl. Med. 2020; 12eabd3876View in Article- Wang E.Y.
- et al.
Diverse functional autoantibodies in patients with COVID-19.
Nature. 2021; 595: 283-288View in Article- Arunachalam P.S.
- et al.
Systems vaccinology of the BNT162b2 mRNA vaccine in humans.
Nature. 2021; 596: 410-416View in Article- Terpos E.
- et al.
Third dose of the BNT162b2 vaccine results in very high levels of neutralizing antibodies against SARS-CoV-2: results of a prospective study in 150 health professionals in Greece.
Am. J. Hematol. 2022; 97: E147-E150View in Article- Wheatley A.K.
- et al.
Immune imprinting and SARS-CoV-2 vaccine design.
Trends Immunol. 2021; 42: 956-959- Röltgen K.
Immune imprinting, breadth of variant recognition and germinal center response in human SARS-CoV-2 infection and vaccination.
Cell. 2022; 185: 1025-1040View in Article- Deshotels M.R.
- et al.
Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism.
Hypertension. 2014; 64: 1368-1375View in Article- Ramos S.G.
- et al.
ACE2 Down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among COVID-19 patients.
Am. J. Pathol. 2021; 191: 1154-1164View in Article- Yeung M.L.
- et al.
Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin–angiotensin system.
Cell. 2021; 184: 2212-2228- Ferrario C.M.
- et al.
Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2.
Circulation. 2005; 111: 2605-2610View in Article- Yang J.
- et al.
Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.
Proc. Natl. Acad. Sci. U. S. A. 2016; 113: E5628-E5635View in Article- McCracken I.R.
- et al.
Lack of evidence of angiotensin-converting enzyme 2 expression and replicative infection by SARS-CoV-2 in human endothelial cells.
Circulation. 2021; 143: 865-868View in Article- Nicosia R.F.
- et al.
COVID-19 vasculopathy: mounting evidence for an indirect mechanism of endothelial injury.
Am. J. Pathol. 2021; 191: 1374-1384- Coate K.C.
- et al.
SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 are expressed in the microvasculature and ducts of human pancreas but are not enriched in β cells.
Cell Metab. 2020; 32: 1028-1040View in Article- Nuovo G.J.
- et al.
Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein.
Ann. Diagn. Pathol. 2021; 51151682View in Article- Lei Y.
- et al.
SARS-CoV-2 spike protein impairs endothelial function via downregulation of ACE 2.
Circ. Res. 2021; 128: 1323-1326View in Article- Raghavan S.
- et al.
SARS-CoV-2 spike protein induces degradation of junctional proteins that maintain endothelial barrier integrity.
Front Cardiovasc. Med. 2021; 8687783View in Article- Colunga Biancatelli R.M.L.
- et al.
The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells.
Am. J. Physiol. Lung Cell Mol. Physiol.2021; 321: L477-L484View in Article- Avolio E.
- et al.
The SARS-CoV-2 spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease.
Clin. Sci. (Lond.). 2021; 135: 2667-2689View in Article- Panigrahi S.
- et al.
SARS-CoV-2 spike protein destabilizes microvascular homeostasis.
Microbiol. Spectr. 2021; 9e0073521View in Article- Clausen T.M.
- et al.
SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2.
Cell. 2020; 183: 1043-1057- Partridge L.J.
- et al.
ACE2-independent interaction of SARS-CoV-2 spike protein with human epithelial cells is inhibited by unfractionated heparin.
Cells. 2021; 10: 1419View in Article- Zheng Y.
- et al.
SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate.
Int. J. Biol. Macromol. 2021; 193: 1124-1129View in Article- Zhang S.
- et al.
SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19.
J. Hematol. Oncol. 2020; 13: 120View in Article- Jana S.
- et al.
Cell-free hemoglobin does not attenuate the effects of SARS-CoV-2 spike protein S1 subunit in pulmonary endothelial cells.
Int. J. Mol. Sci. 2021; 22: 9041View in Article- Ryu J.K.
- et al.
SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy.
bioRxiv. 2021; (Published online October 13, 2021)View in Article- Terpos E.
- et al.
High prevalence of anti-PF4 antibodies following ChAdOx1 nCov-19 (AZD1222) vaccination even in the absence of thrombotic events.
Vaccines. 2021; 9: 712View in Article- Cattin-Ortolá J.
- et al.
Sequences in the cytoplasmic tail of SARS-CoV-2 spike facilitate expression at the cell surface and syncytia formation.
Nat. Commun. 2021; 12: 5333View in Article- Rajah M.M.
- et al.
SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced spike-mediated syncytia formation.
EMBO J. 2021; 40e108944View in Article- Cheng Y.-W.
- et al.
D614G substitution of SARS-CoV-2 spike protein increases syncytium formation and virus titer via enhanced furin-mediated spike cleavage.
mBio. 2021; 12e0058721View in Article- Correa Y.
- et al.
SARS-CoV-2 spike protein removes lipids from model membranes and interferes with the capacity of high-density lipoprotein to exchange lipids.
J. Colloid Interface Sci. 2021; 602: 732-739View in Article- Jiang H.
- Mei Y.-F.
SARS-CoV-2 spike impairs DNA damage repair and inhibits V(D)J recombination in vitro.
Viruses. 2021; 13: 2056View in Article- Lai Y.-J.
- et al.
Epithelial–mesenchymal transition induced by SARS-CoV-2 required transcriptional upregulation of Snail.
Am. J. Cancer Res. 2021; 11: 2278-2290View in Article- Hsu J.T.-A.
- et al.
The effects of Aβ(1–42) binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2.
Int. J. Mol. Sci. 2021; 22: 8226View in Article- Chen R.
- et al.
The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in the human and mouse brains.
Front. Neurol. 2020; 11573095View in Article- Rhea E.M.
- et al.
The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice.
Nat. Neurosci. 2021; 24: 368-378View in Article- DeOre B.J.
- et al.
SARS-CoV-2 spike protein disrupts blood–brain barrier integrity via RhoA activation.
J. NeuroImmune Pharmacol. 2021; 16: 722-728View in Article- Welch J.L.
- et al.
T-cell expression of angiotensin-converting enzyme 2 and binding of severe acute respiratory coronavirus 2.
J. Infect. Dis. 2022; 225: 810-819View in Article- Barreda D.
- et al.
SARS-CoV-2 spike protein and its receptor binding domain promote a proinflammatory activation profile on human dendritic cells.
Cells. 2021; 10: 3279View in Article- Maldonado M.D.
- Romero-Aibar J.
The Pfizer-BNT162b2 mRNA-based vaccine against SARS-CoV-2 may be responsible for awakening the latency of herpes varicella-zoster virus.
Brain Behav. Immun. Health. 2021; 18100381View in Article- Psichogiou M.
- et al.
Reactivation of varicella zoster virus after vaccination for SARS-CoV-2.
Vaccines. 2021; 9: 572View in Article- Kim E.S.
- et al.
Spike proteins of SARS-CoV-2 induce pathological changes in molecular delivery and metabolic function in the brain endothelial cells.
Viruses. 2021; 13: 2021View in Article- Kumar N.
- et al.
SARS-CoV-2 spike protein S1-mediated endothelial injury and pro-inflammatory state is amplified by dihydrotestosterone and prevented by mineralocorticoid antagonism.
Viruses. 2021; 13: 2209View in Article- Rahman M.
- et al.
Differential effect of SARS-CoV-2 spike glycoprotein 1 on human bronchial and alveolar lung mucosa models: implications for pathogenicity.
Viruses. 2021; 13: 2537View in Article- Li F.
- et al.
SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling.
Biochim. Biophys. Acta Mol. basis Dis.2021; 1867166260View in Article- Meyer K.
- et al.
SARS-CoV-2 spike protein induces paracrine senescence and leukocyte adhesion in endothelial cells.
J. Virol. 2021; 95e0079421View in Article- Zhu G.
- et al.
SARS-CoV-2 spike protein-induced host inflammatory response signature in human corneal epithelial cells.
Mol. Med. Rep. 2021; 24: 584View in Article- Ntouros P.A.
- et al.
Effective DNA damage response after acute but not chronic immune challenge: SARS-CoV-2 vaccine versus systemic lupus erythematosus.
Clin. Immunol. 2021; 229108765View in Article- Petruk G.
- et al.
SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity.
J. Mol. Cell Biol. 2020; 12: 916-932View in Article- Tumpara S.
- et al.
Boosted pro-inflammatory activity in human PBMCs by LIPOPOLYSACCHARIDE and SARS-CoV-2 spike protein is regulated by α-1 antitrypsin.
Int. J. Mol. Sci. 2021; 22: 7941View in Article- Olajide O.A.
- et al.
SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia.
Mol. Neurobiol. 2022; 59: 445-458View in Article- Moutal A.
- et al.
SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia.
Pain. 2021; 162: 243-252View in Article- Khan S.
- et al.
SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway.
eLife. 2021; 10e68563View in Article- Cheng M.H.
- et al.
Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation.
Proc. Natl. Acad. Sci. U. S. A. 2020; 117: 25254-25262View in Article- Cao X.
- et al.
Spike protein of SARS-CoV-2 activates macrophages and contributes to induction of acute lung inflammation in male mice.
FASEB J. 2021; 35e21801View in Article- Frank M.G.
- et al.
SARS-CoV-2 spike S1 subunit induces neuroinflammatory, microglial and behavioral sickness responses: evidence of PAMP-like properties.
Brain Behav. Immun. 2022; 100: 267-277View in Article- Bergamaschi C.
- et al.
Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients.
Cell Rep. 2021; 36109504- Au L.
- et al.
Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2.
Nat. Med. 2021; 27: 1362-1366View in Article- Camell C.D.
- et al.
Senolytics reduce coronavirus-related mortality in old mice.
Science. 2021; 373eabe4832View in Article- Kowalzik F.
- et al.
mRNA-based vaccines.
Vaccines. 2021; 9: 390View in Article- Racanelli V.
- Rehermann B.
The liver as an immunological organ.
Hepatology. 2006; 43: S54-S62View in Article- Horst A.K.
- et al.
Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells.
Cell. Mol. Immunol. 2016; 13: 277-292View in Article- Avci E.
- Abasiyanik F.
Autoimmune hepatitis after SARS-CoV-2 vaccine: new-onset or flare-up?.
J. Autoimmun. 2021; 125102745View in Article- Zin Tun G.S.
- et al.
Immune-mediated hepatitis with the Moderna vaccine, no longer a coincidence but confirmed.
J. Hepatol. 2021; 76: 747-749- Harryvan T.J.
- et al.
The ABCs of antigen presentation by stromal non-professional antigen-presenting cells.
Int. J. Mol. Sci. 2021; 23: 137View in Article- Carnell G.W.
- et al.
SARS-CoV-2 spike protein stabilized in the closed state induces potent neutralizing responses.
J. Virol. 2021; 95e0020321View in Article- Hoffmann M.
- et al.
SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.
Cell. 2020; 181: 271-280- Lan J.
- et al.
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Nature. 2020; 581: 215-220View in Article- Piroth L.
- et al.
Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study.
Lancet Respir. Med. 2021; 9: 251-259- Castagnoli R.
- et al.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review.
JAMA Pediatr. 2020; 174: 882-889View in Article- Goldstein E.
- et al.
On the effect of age on the transmission of SARS-CoV-2 in households, schools, and the community.
J. Infect. Dis. 2021; 223: 362-369View in Article- Yoshida M.
- et al.
Local and systemic responses to SARS-CoV-2 infection in children and adults.
Nature. 2022; 602: 321-327View in Article- Killingley B.
- et al.
Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.
Nat Med. 2022; (Published online March 31, 2022)View in Article- Zhang J.-Y.
- et al.
Single-cell landscape of immunological responses in patients with COVID-19.
Nat. Immunol. 2020; 21: 1107-1118View in Article- Low J.S.
- et al.
Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2.
Science. 2021; 372: 1336-1341View in Article- Cagigi A.
- et al.
Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination.
JCI Insight. 2021; 6e151463View in Article- Loske J.
- et al.
Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children.
Nat. Biotechnol. 2021; 40: 319-324View in Article- See I.
- et al.
US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021.
JAMA. 2021; 325: 2448-2456View in Article- Reimer J.M.
- et al.
Matrix-MTM adjuvant induces local recruitment, activation and maturation of central immune cells in absence of antigen.
PLoS One. 2012; 7e41451View in Article
Glossary
Acute respiratory distress syndrome (ARDS)a life-threatening condition in which fluid builds up in the lungs, interfering with the gas exchange function and preventing oxygenation of the blood and organs.
Adverse effect (AE)an undesired effect of a medication or clinical intervention with potentially harmful consequences.
Angiotensin-converting enzyme 2 (ACE2)an enzyme involved in the homeostatic regulation of circulating angiotensin I and angiotensin II levels by converting them to angiotensin (1–9) and angiotensin (1–7) peptides respectively.
Bell’s palsyan idiopathic episode of facial muscle weakness or paralysis on one side of the face. This condition results from dysfunction of the seventh cranial nerve (the facial nerve).
Cerebral venous sinus thrombosisa rare blood-clotting event that occurs in the venous sinuses of the brain and prevents blood from draining out of the brain. As a result, pressure builds up and can lead to swelling and hemorrhage.
Cytokine storma characteristic of COVID-19 (or other disease) where abnormally high levels of circulating cytokines are produced and contribute to disease severity.
Guillain–Barré syndromea rare, autoimmune neurological disorder in which the body's immune system erroneously attacks the peripheral nerves, causing muscle weakness and, if left untreated, paralysis.
Long COVID-19a term that refers to a range of new, returning, or ongoing symptoms that persist beyond the initial phase of a SARS-CoV-2 infection.
Molecular mimicrythe process in which an immune response against a foreign antigen is inadvertently also directed against a self-antigen that closely resembles the triggering foreign antigen.
Receptor-binding domain (RBD)the part of a binding protein (e.g., in SARS-CoV-2 S protein) used to anchor the protein to its receptor.
Renin–angiotensin system (RAS)a system that is critical in the physiological regulation of (among others) neural, gut, cardiovascular, blood pressure, and kidney functions, as well as fluid and salt balance. It involves the enzyme renin which catalyzes the production of angiotensin I.
Serological analysisany analysis performed with blood serum, usually focusing on measuring antibody levels.
Syncytiuma cell with multiple nuclei resulting from multiple fusions of uninuclear cells.
Viremiathe detection of replication-competent viral particles in the bloodstream.
Article info
Publication history
Published online: April 20, 2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectFigures
Figure 1Key figure. Antigen expression–localization following cell transfection with spike (S) protein mRNA-containing lipid nanoparticles (LNPs) used in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines.
Figure 2Schematic of the vasculature components showing vaccination-produced S protein/subunits/peptide fragments in the circulation, as well as soluble or endothelial cell membrane-attached angiotensin-converting enzyme 2 (ACE2).
No comments:
Post a Comment