Viral master stocks (2 107 PFU/ml) were grown in Vero E6 cells as previously described33. This site uses cookies. Icahn School of Medicine at Mount Sinai. PBMCs were isolated by Ficoll-Hypaque (Amersham Biosciences) density gradient centrifugation and cryopreserved before subsequent analysis. Background Early-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. 3a). 2004 Dec 2;23(3):362-5. doi: 10.1016/j.vaccine.2004.05.035. Accessed Nov. 15, 2022. Two doses of 150g of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. 11, 6571 (2020). Arrowheads indicate days of vaccinations. A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation. Some studies have found higher CRP levels in males with anxiety disorder, although it's not clear that anxiety causes high CRP levels. She had normal CBC, CRP, creatinine, estimated GFR (78 mL/min) and urinalysis. 2021 Feb;590(7844):E17. a, Correlation of RBD-specific IgG responses (as in Fig. d, Cytokine release by PBMCs from the 50g cohort (n=5; assay results from remaining samples of this and other cohorts not available at the time). This study now complements and expands our previous report with available data from the German trial (NCT04380701, EudraCT: 2020-001038-36), providing a detailed characterization of antibody and T cell immune responses elicited by vaccination with BNT162b1. Should she receive a second dose but not an mRNA vaccine? Accessed Nov. 15, 2022. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. The only abnormalities were hemoglobin A1C at 6.2%, mildly elevated total cholesterol and TG. Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. A.B., D.C., M.C., C.F.-G., W.K., K.P., J.Q., I.L.S. The mRNA is formulated with lipids to obtain the RNALNP drug product. Each serum was tested in duplicate and GMT plotted. Among participants who showed any vaccine-induced CD8+ T cell response (32/42 participants receiving the prime-boost dosing, 76.2%), the majority mounted strong responses (Fig. Although there were no relevant changes in routine clinical laboratory values after vaccination with BNT162b1, vaccinated participants showed a transient increase in C-reactive protein (CRP) and a temporary reduction in blood lymphocyte counts, both of which were dose-dependent (Extended Data Fig. Serum for antibody assays was obtained on days 1 (pre-prime), 81 (post-prime), 222 (pre-boost), 293 and 434 (post-boost). Read more about. Her photos show a diffuse maculopapular rash. Erratum in: Nature. Controls were treated with DMSO-containing medium. The second dose was fine. To provide you with the most relevant and helpful information, and understand which Another constraint is that we did not perform further T cell analysis (for example, deconvolution of epitope diversity, characterization of HLA restriction, T cell phenotyping and TCR repertoire analysis) before and after vaccination, because of the limited blood volumes that were available for biomarker analyses. Follow along on Facebook and join the lively conversation! Trials that tested the BNT162b2 and mRNA-1273 vaccines showed that systemic reactogenicity more often occurred after dose 2 and generally within 48 hours after vaccination. ADS However, diet and exercise may also lower your levels. Vero cells (CCL-81) and Vero E6 cells (ATCC CRL-1586) were sourced from the American Type Culture Collection (ATCC), which maintains a quality management system commensurate to ISO 9001:2015, ISO 13485:2016, ISO 17025:2017, and ISO 17034:2016. Med. Medical content developed and reviewed by the leading experts in allergy, asthma and immunology. The antigen-encoding RNA contains sequence elements that increase RNA stability and translation efficiency in human dendritic cells13,14. 2019; doi:10.1161/CIR.0000000000000678. Influenza and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation. Vaccine. Mayo Clinic College of Medicine and Science, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Graduate Medical Education, Mayo Clinic School of Continuous Professional Development, Mayo Clinic on Incontinence - Mayo Clinic Press, NEW Mayo Clinic on High Blood Pressure - Mayo Clinic Press, Mayo Clinic on Hearing and Balance - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press, Financial Assistance Documents Minnesota. We do not have Johnson & Johnson vaccine in Canada. How can one naturally lower an elevated CRP count? It measures very low amounts of CRP, with a focus on cardiac risk and prevention of heart-related disease. Checked bars indicate that no boost vaccination was performed. An Infectious cDNA Clone of SARS-CoV-2. The clinical trial protocol for BNT162b1. Moderate elevation refers to levels between 1.0 mg/dl and 10.0 mg/dl, which can signal a more significant issue. information is beneficial, we may combine your email and website usage information with Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 1855 years of age. Study BNT162-01 (NCT04380701) is an ongoing, first-in-human, phase I/II, open-label dose-ranging clinical trial to assess the safety, tolerability, and immunogenicity of ascending dose levels of various intramuscularly administered BNT162 mRNA vaccine candidates in healthy men and non-pregnant women 18 to 55 years of age (amended to add 5685 years of age). were responsible for biomarker and R&D program management. Immunology of COVID-19: current state of the science. C-reactive protein, high sensitivity, serum. c, RBD-specific CD8+ (top) or CD4+ (bottom) T cells producing the indicated cytokine as a percentage of total circulating T cells of the same subset. 2c, Extended Data Table 5). The pVNT50 was reported as the interpolated reciprocal of the dilution yielding a 50% reduction in fluorescent viral foci. Serum was obtained on day 1 (pre-prime), 81 (post-prime), 222 (pre-boost), 293 and 434 (post-boost). The next day the tests were repeated and same results were seen. Studies have shown that they can reduce CRP levels by 13% to 50%. Those with elevated CRP may benefit from aspirin therapy more than people whose CRP levels are normal. volume586,pages 594599 (2020)Cite this article, A Publisher Correction to this article was published on 19 January 2021. The next evening, she developed a fever (39C). New vaccine technologies to combat outbreak situations. It was not checked previously. Med. The reaction included fever, generalized maculopapular rash, likely ankle arthritis, generalized edema, associated with lymphopenia, impaired kidney function (low GFR and hypokalemia) and elevated CRP. In this assay, CD4+ or CD8+ T cell effectors were stimulated overnight with overlapping peptides representing the full-length sequence of the vaccine-encoded RBD. Holtkamp, S. et al. Aspirin and heart disease. There is a problem with To obtain COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Increased serum amyloid A (SAA) APR predicted severe vascular disease. About 72 hours after her COVID-19 shot, she developed non-itchy papules on her neck which over the next couple days spread all over her body. Nat. r=0.48, P=0.0057. c, Correlation of CD4+ with CD8+ T cell responses (n=51 as in Fig. By submitting a comment you agree to abide by our Terms and Community Guidelines. Purely RBD-directed immunity might be considered prone to escape of the virus by single amino-acid changes in this small domain. Lab tests when she first became symptomatic showed high CRP (40 mg/ L; normal<3), high creatinine and low estimated GFR (53 mL/min), Lymphopenia (0.6 X 10 9/ L), mild hypokalemia (3.3), mild elevation in LDH, mildly reduced serum albumin at 32 g/ L (her baseline is 43). Looking for the very latest from Dr. Weil on a variety of topics, including healthy living, longevity, well-being, recipes, and healthy diets as well as photos of his daily life, garden, and wellness travels? All participants provided written informed consent. analysed data. This build-up can narrow the arteries that feed the heart blood, causing coronary artery disease (CAD). Chong, W. P. et al. Risk Assessment for Cardiovascular Disease With Nontraditional Risk Factors: US Preventive Services Task Force Recommendation Statement. Further information on research design is available in theNature Research Reporting Summary linked to this paper. advised on experiments. Elevated CRP levels in the blood are a sign of inflammation. No history of viral illnesses or other vaccines in this April or May. a, RBD-specific CD4+ and CD8+ T cell responses for each dose cohort. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. Most participants were white (96.7%) with one African American and one Asian participant (1.7% each; Extended Data Table 1). With patient convalescent sera, the fluorescent neutralization assay produced comparable results to the conventional plaque reduction neutralization assay34. Med. U.S. Preventive Services Task Force, Curry SJ, Krist AH, et al. PMID: 10852144. https://pubmed.ncbi.nlm.nih.gov/10852144/, Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, Baum A, Pascal K, Quandt J, Maurus D, Brachtendorf S, Lrks V, Sikorski J, Hilker R, Becker D, Eller AK, Grtzner J, Boesler C, Rosenbaum C, Khnle MC, Luxemburger U, Kemmer-Brck A, Langer D, Bexon M, Bolte S, Karik K, Palanche T, Fischer B, Schultz A, Shi PY, Fontes-Garfias C, Perez JL, Swanson KA, Loschko J, Scully IL, Cutler M, Kalina W, Kyratsous CA, Cooper D, Dormitzer PR, Jansen KU, Treci . This is known as intermediate risk. Kamphuis, E., Junt, T., Waibler, Z., Forster, R. & Kalinke, U. Between 23 April 2020 and 22 May 2020, 60 participants were vaccinated with BNT162b1 in Germany. Bound IFN was visualized using a secondary anti-IFN antibody directly conjugated with alkaline phosphatase (1:250; ELISpotPro kit, Mabtech) followed by incubation with a 5-bromo-4-chloro-3-indolyl phosphate (BCIP)/nitro blue tetrazolium (NBT) substrate (ELISpotPro kit, Mabtech). The next evening, she developed a fever (39C). PBMCs for T cell studies were obtained on days 1 (pre-prime) and 293 (post-boost). Sahin, U. et al. U.S. Preventive Task Force. and M.V. In premature infants, CRP level increased in response to the simultaneous administration of the diphtheria, tetanus and whole-cell pertussis vaccine, Haemophilus influenza type b conjugate. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. It explains CRP blood tests, possible causes for high CRP levels, and the medication and lifestyle changes that may be used to treat it. You can return to your usual activities right away. 1, 2 On average, our patients presented with symptoms of acute myocarditis 3 days after the second injection, and in 5 out of 8 patients fever appeared a day before, Interferon- was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. Function of C-reactive protein. Ann Med. It's best if they're taken two weeks apart. Objectives To identify an appropriate range of CRP values in healthy . Anxiety disorders and inflammation in a large adult cohort. PubMed Results equal to or greater than 8 mg/L or 10 mg/L are considered high. Negative values were set to zero. Spearman correlation was used to evaluate the monotonic relationship between non-normally distributed data sets. At present, there is probably insufficient immunity to SARS-CoV-2 in the human population to drive antigenic drift. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Taking steps to make your lifestyle healthier can also help. 2). To address this concern, we conducted neutralization assays with 17 pseudotyped viruses, 16 of which enter cells using a spike with a different RBD variant found in circulating strains and one of which uses the dominant spike variant D614G. Sign up for the Nature Briefing: Translational Research newsletter top stories in biotechnology, drug discovery and pharma. Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response. Serial dilutions of heat-inactivated sera were incubated with the reporter virus (2 104 PFU per well to yield a 1030% infection rate of the Vero CCL81 monolayer) for 1 h at 37C before inoculating Vero CCL81 cell monolayers (targeted to have 8,000 to 15,000 cells in a central field of each well at the time of seeding, 24h before infection) in 96-well plates to allow accurate quantification of infected cells. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. All study data were available to all authors. Having a high hs-CRP level doesn't always mean a higher risk of developing heart disease. At 24 h post-transfection at 37C, cells were infected with the VSVG:mNeon/VSV-G diluted in Opti-MEM (Life Technologies) at a multiplicity of infection of 1. The final assay results were expressed as the GMC of all sample dilutions that produced a valid assay result within the assay range. Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells. When you have an infection, the white blood cells act to fight it by producing a number of proteins, some of which stimulate the liver to produce CRP. Nat. Response definition criteria for ELISPOT assays revisited. Narrowed arteries can lead to a heart attack. PBMCs thawed and rested for 4h in OpTmizer medium supplemented with 2 g/ml DNase I (Roche) were restimulated with a peptide pool representing the vaccine-encoded SARS-CoV-2 RBD (2 g/ml/peptide; JPT Peptide Technologies) in the presence of GolgiPlug (BD) for 18 h at 37C. Thank you, {{form.email}}, for signing up. Preprint at https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1 (2020). What constitutes a "high" level varies from person to person, but a reading of 2 milligrams per liter or above is often considered a dangerous CRP level and puts you at risk for a heart attack. In general, anything above 1 mg/dL is elevated and may require intervention. Is that true, and is it dangerous? PBMCs from vaccinated participants (7 days after boost for cohorts 1 and 10g, n=10 each; 30g, n=12; 50g, n=9; 28 days after prime for the 60g cohort, n=11) and donors who had recovered from COVID-19 (HCS, n=15; c) were stimulated over night with an overlapping peptide pool representing the vaccine-encoded RBD and analysed by flow cytometry (ac) and bead-based immunoassay (d). information submitted for this request. Int. It remains unknown whether CRP itself increases cardiovascular risk. Intrafamilial exposure to SARS-CoV-2 induces cellular immune response without seroconversion. Eosinophilia occurs when a large number of eosinophils are recruited to a specific site in your body or when the bone marrow produces too many eosinophils. Three days after vaccination, she experienced fevers, headaches, abdominal pain, fatigue, and myalgias. 6, 82 (2006). https://www.uptodate.com/contents/search. Your health care provider might order a C-reactive protein test to: A high level of hs-CRP in the blood has been linked to an increased risk of heart attacks. D.M. Cytokine production in Fig. A study of 376 people found that 210 of them diagnosed with CAD all had elevated CRP levels when compared with 166 people who did not have CAD. A.B., C.A.K. She received her first dose of Pfizer COVID-19 shot on May 9. Environ. 1. C-reactive protein is measured in milligrams per liter (mg/L). Similar to the USA trial, most of the reported solicited systemic events in the 10-g and 30-g groups were due to reactogenicity, with a typical onset within the first 24h of immunization (Extended Data Fig. J. Occup. The associated symptomatology, such as fever, chills, headache, muscle pain, joint pain, injection site pain, and tenderness, was mostly mild or moderate, with occasional severe (grade 3) manifestations. No history of reaction to medications or vaccines in the past, except she developed a fever after she got the first dose of Shingrix vaccine. Tai, W. et al. Commun. ADS other information we have about you. Taylor, D. N. et al. Although there were no relevant changes in routine clinical laboratory values after vaccination with BNT162b1, vaccinated participants showed a transient increase in C-reactive protein. Immunity 52, 910941 (2020). The vaccination schedule is described in Extended Data Fig. By continuing to browse this site, you are agreeing to our use of cookies. Each data point represents the normalized mean spot count from duplicate wells for one study participant, after subtraction of the medium-only control (a, c). C-reactive protein in cardiovascular disease. 2012;13(3):153-61. doi:10.1310/hct1303-153. For values below the lower limit of quantification (LLOQ)=1.15, LLOQ/2 values were plotted. JAMA 2018; 320:272. 3 mg/L on Sept 9, 2020), and erythrocyte sedimentation rate . Concentrations of RBD-binding IgG and SARS-CoV-2-neutralizing titres were assessed at baseline, 7 and 21days after the BNT162b1 priming dose (days 8 and 22), and 7 and 21 days after the boost dose (days 29 and 43), except for the 60-g cohort, which received a priming dose only (Fig. You can lower your CRP levels by adopting a healthy lifestyle and, if appropriate, taking a statin. Each serum was tested in duplicate and GMT plotted. For pseudovirus neutralization assays, Vero cells (ATCC CCL-81) were seeded in 96-well plates in culture medium and allowed to reach approximately 85% confluence before use in the assay (24h later). The RNA is optimized for high stability and translation efficiency13,14 and incorporates 1-methylpseudouridine instead of uridine to dampen innate immune sensing and to increase mRNA translation in vivo15. CDC has published studies with clinical information about myocarditis and pericarditis after COVID-19 vaccination. IFN ELISpot analysis was performed ex vivo (without further in vitro culturing for expansion) using PBMCs depleted of CD4+ and enriched for CD8+ T cells (CD8+ effectors), or depleted of CD8+ and enriched for CD4+ T cells (CD4+ effectors). On day 43 (21 days after boost), RBD-binding antibody GMCs were in the range of 3,92018,289 Uml1 in BNT162b1-vaccinated individuals, as compared to a GMC of 602Uml1 measured in a panel of convalescent sera from 38 patients who had been infected with SARS-CoV-2. 4. Vaccine 34, 20082014 (2016). Arithmetic mean with 95% CI. When CRP levels remain elevated for a long time, it can indicate chronic inflammation of the blood vessels. It is also not the same as dangerously high levels of CRP seen as a result of infection with the coronavirus itself. Vaccine 37, 18191826 (2019). Lab. Front. She is generally healthy. You can find out more about our use, change your default settings, and withdraw your consent at any time with effect for the future by visiting Cookies Settings, which can also be found in the footer of the site. I would recommend shared decision making with the patient regarding whether a second dose of the mRNA vaccine should be provided or not. One individual in the 10g cohort and one in the 50g cohort left the study before the boosting immunization owing to withdrawal of consent for private reasons. All 15 had elevated plasma viscosity as assessed by capillary viscometry (range, 1.9 to 4.2 centipoise [cP]; normal range, 1.4 to 1.8 cP). An elevated level of CRP is considered an increased risk for heart disease, and testing CRP levels is often part of cardiac care. Science 369, 10141018 (2020). The blood tests are almost normal now (3 months later). 4c). A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03102-w. Mulligan, M. J. et al. These criteria include being younger than 21 years, fever for over three consecutive days, pericardial effusion, elevated C-reactive protein (CRP)/N-terminal B-type natriuretic peptide. 2020 Oct;586(7830):594-599. doi: 10.1038/s41586-020-2814-7. 1 Schedule of vaccination and assessment. In: Ferri's Best Test: A Practical Guide to Clinical Laboratory Medicine and Diagnostic Imaging. CRP stands forC-reactive protein, which is produced by the liver and regarded as a general indicator of inflammation in the body. Reproduction in whole or in part without permission is prohibited. Cells were certified by the vendor and cultured in Dulbeccos modified Eagles medium (DMEM) with GlutaMAX (Gibco) supplemented with 10% fetal bovine serum (FBS) (Sigma-Aldrich). Two phaseI/II umbrella trials in Germany and the USA are investigating several LNP-encapsulated RNA vaccine candidates developed in Project Lightspeed, the joint BioNTech-Pfizer COVID-19 RNA vaccine development program. 215, 15711588 (2018). Your health care provider can explain what the test results mean. Nov. 16, 2022. The fever lasted a few days and the rash for about a week. Participants received a BNT162b1 prime dose on day 1, and a boost dose on day 222. Thank you for visiting nature.com. The bottom line is that a temporary elevation in CRP level is to be expected after a vaccine. Higher levels of C reactive protein (CRP) may be a predictive marker in determining which patients with mild coronavirus disease 2019 (COVID-19) will progress to a severe case, according to study results published in Open Forum Infectious Diseases. 1998-2023 Mayo Foundation for Medical Education and Research (MFMER). and T.P. Sette, A. et al. Baum, A. et al. It can take a few days to get results. You may have your CRP levels checked if your healthcare provider thinks you could have an infection or another inflammation-causing condition. In addition, infection with SARS-CoV-2 might elicit neutralizing antibodies that recognize epitopes that are exposed on virions and located outside the RBD, differentially increasing the serum neutralizing GMT after infection29,30. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. In the placebo-controlled, observer-blinded USA trial, dosages of 10g, 30g (prime and boost doses 21days apart for both dose levels) and 100g (prime only) were administered. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. Cytokine-producing T cells were identified by intracellular cytokine staining. J Clin Med Res. Selective CD4+ T cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities. and K.A.S. It is notable that there are other factors that can elevate CRP levels. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Virology 329, 1117 (2004). Correspondence to doi:10.1161/CIR.0000000000000677. For values below the lower limit of quantification (LLOQ)=0.3, LLOQ/2 values were plotted (a). r=0.4829, P=0.0014. b, Correlation of VNT50 (as in Fig. High CRP in COVID-19 is associated with complications of the coronavirus, including venous thromboembolism, acute kidney injury, critical illness, and mortality. Rauch, S., Jasny, E., Schmidt, K. E. & Petsch, B. Medicine. Renal disease, female sex and older age . Of 42 participants who had received primeboost vaccination (the 1g to 50g cohorts), 40 (95.2%, including all participants treated with10g BNT162b1 or more) mounted RBD-specific CD4+ T cell responses. Several types of cancer are among the diseases that can cause c-reactive protein to be elevated. In addition, some published reports are limited to follow-up after a single vaccine dose. Fractions of RBD-specific IFN+ CD8+ T cells reached up to several per cent of total peripheral blood CD8+ T cells in immunized individuals (Fig. A transient increase in CRP levels has also been observed after other vaccines, including those for influenza and pneumococcalpneumonia. High CRP in COVID-19 is associated with complications of the coronavirus, including venous thromboembolism, acute kidney injury, critical illness, and mortality. The ratio of serum virus neutralization GMT to recombinant RBD-binding IgG GMC is lower after immunization with BNT162b1 than after infection with SARS-CoV-2. are management board members and employees at BioNTech SE (Mainz, Germany); D.B., C.B., S. Brachtendorf, E.D., A.-K.E., B.F., J.G., R.H., M.-C.K., U.L., V.L., D.M., C.R., J.S. The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Walsh, E. E. et al. Brouwer, P. J. M. et al. All Rights Reserved. You should not use the information on this website for diagnosing or treating a health problem or disease, or prescribing any medication or other treatment. Nature 586, 594599 (2020). 59, 14891501 (2010). Blood 108, 40094017 (2006). Release 217, 345351 (2015). Moodie, Z., Huang, Y., Gu, L., Hural, J. You can also find him on Instagram and Twitter. Immunol. Seven days after the boosting dose (day 29), RBD-binding IgG GMCs in participants vaccinated with 150 g BNT162b1 showed a strong, dose-dependent booster response ranging from 2,015 to 25,006Uml1. 2020 Aug;103(2):561-563. doi: 10.4269/ajtmh.20-0473. doi:10.1097/md.0000000000007822. c, RBD-specific CD4+ and CD8+ T cell-responses in all participants who received prime and boost vaccination (n=42) with a positive response to RBD and their baseline CEFT- and CEF-specific T cell responses. planned and supervised dashboards for analysis of clinical trial data. This content does not have an Arabic version. is an officer at Regeneron Pharmaceuticals, Inc; A.B., C.A.K. Neutralization titres were calculated in GraphPad Prism version 8.4.2 by generating a 4PL fit of the percentage neutralization at each serial serum dilution. Vaccination schedule and serum sampling are described in Extended Data Fig. These strategies can help lower your CRP levels and potentially reduce your cardiovascular risk. Our website is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Experiments were planned or supervised by E.D., C.F.-G., C.A.K., L.M.K., U.L., A.M., J.Q., P.-Y.S. Vogelzangs N, Beekman AT, de Jonge P, Penninx BW. No serious adverse events were reported. Mitchell Grayson, MD, FAAAAI. Peer review information Nature thanks Barbra Richardson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. This may involve habit changes, weight loss efforts, and/or medication. Fluorescence was measured with a Bioplex200 system (Bio-Rad) and analysed with ProcartaPlex Analyst 1.0 software (Thermo Fisher Scientific). 4b). 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