{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:02:27Z","timestamp":1772794947056,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to cross-reacting material CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Haemophilus influenzae type b (Hib) and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.<\/jats:p>","DOI":"10.3390\/vaccines8040559","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T08:33:03Z","timestamp":1600936383000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Possible Cross-Reactivity between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3298-9306","authenticated-orcid":false,"given":"Robert","family":"Root-Bernstein","sequence":"first","affiliation":[{"name":"Department of Physiology, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Root-Bernstein, R. (2020). Age and Location in Severity of COVID-19 Pathology: Do Lactoferrin and Pneumococcal Vaccination Explain Low Infant Mortality and Regional Differences?. BioEssays.","DOI":"10.1002\/bies.202000076"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pawlowski, C., Puranik, A., Bandi, H., Venkatakrishnan, A.J., Agarwal, V., Kennedy, R., O\u2019Horo, J.C., Gores, G.J., Williams, A.W., and Halamka, J. (2020). Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations. medRxiv.","DOI":"10.1101\/2020.07.27.20161976"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Watanabe, Y., Allen, J.D., Wrapp, D., McLellan, J.S., and Crispin, M. (2020). Site-specific glycan analysis of the SARS-CoV-2 spike. Science, eabb9983.","DOI":"10.1101\/2020.03.26.010322"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Shajahan, A., Supekar, N.T., Gleinich, A., and Azadi, P. (2020). Deducing the N- and O-glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2. Glycobiology.","DOI":"10.1101\/2020.04.01.020966"},{"key":"ref_5","unstructured":"WHO (2009). Recommendations to Assure the Quality, Safety and Efficacy of Pneumococcal Conjugate Vaccines, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fbioe.2020.00039","article-title":"Quality Improvement of Capsular Polysaccharide in Streptococcus pneumoniae by Purification Process Optimization","volume":"8","author":"Lee","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Morais, V., Dee, V., and Su\u00e1rez, N. (2018). Purification of Capsular Polysaccharides of Streptococcus pneumoniae: Traditional and New Methods. Front. Bioeng. Biotechnol., 6.","DOI":"10.3389\/fbioe.2018.00145"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1128\/CDLI.6.4.519-524.1999","article-title":"Pneumococcal Capsular Polysaccharide Preparations May Contain Non-C-Polysaccharide Contaminants That Are Immunogenic","volume":"6","author":"Yu","year":"1999","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1086\/368200","article-title":"Immunogenic Protein Contaminants in Pneumococcal Vaccines","volume":"187","author":"Yu","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.1128\/IAI.67.12.6533-6542.1999","article-title":"The pspC Gene of Streptococcus pneumoniae Encodes a Polymorphic Protein, PspC, Which Elicits Cross-Reactive Antibodies to PspA and Provides Immunity to Pneumococcal Bacteremia","volume":"67","author":"Briles","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.1128\/IAI.69.10.5997-6003.2001","article-title":"Protection against Streptococcus pneumoniae Elicited by Immunization with Pneumolysin and CbpA","volume":"69","author":"Ogunniyi","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20488","DOI":"10.1038\/srep20488","article-title":"Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites","volume":"6","author":"Resemann","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/353622a0","article-title":"Sequence analysis of peptides bound to MHC class II molecules","volume":"353","author":"Rudensky","year":"1991","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1093\/intimm\/12.3.375","article-title":"Minimal peptide length requirements for CD4+ T cell clones\u2014Implications for molecular mimicry and T cell survival","volume":"12","author":"Hemmer","year":"2000","journal-title":"Int. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1182\/blood-2012-06-437202","article-title":"Peptide length determines the outcome of TCR\/peptide-MHCI engagement","volume":"121","author":"Miles","year":"2013","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.4049\/jimmunol.143.8.2677","article-title":"Human and murine antibodies cross-reactive with streptococcal M protein and myosin recognize the sequence GLN-LYS-SER-LYS-GLN in M protein","volume":"143","author":"Cunningham","year":"1989","journal-title":"J. Immunol."},{"key":"ref_17","first-page":"65","article-title":"Quantifying the possible cross-reactivity risk of an HPV16 vaccine","volume":"8","author":"Kanduc","year":"2009","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/jmr.930","article-title":"Autoreactive T-cell receptor (Vbeta\/D\/Jbeta) sequences in diabetes are homologous to insulin, glucagon, the insulin receptor, and the glucagon receptor","volume":"22","year":"2009","journal-title":"J. Mol. Recognit."},{"key":"ref_19","first-page":"85","article-title":"Rethinking Molecular Mimicry in Rheumatic Heart Disease and Autoimmune Myocarditis: Laminin, Collagen IV, CAR, and B1AR as Initial Targets of Disease","volume":"2","year":"2014","journal-title":"Front. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2174\/1876894601204010010","article-title":"T Cell Receptor Variable Regions in Diabetes Bind to Each Other, to Insulin, Glucagon or Insulin Receptor, and to Their Antibodies","volume":"4","year":"2012","journal-title":"Open Autoimmun. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.2174\/1871520615666150716105057","article-title":"How to Make a Non-Antigenic Protein (Auto) Antigenic: Molecular Complementarity Alters Antigen Processing and Activates Adaptive-Innate Immunity Synergy","volume":"15","year":"2015","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1373208","DOI":"10.1080\/21688370.2017.1373208","article-title":"Intestinal barrier and gut microbiota: Shaping our immune responses throughout life","volume":"5","author":"Takiishi","year":"2017","journal-title":"Tissue Barriers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1126\/science.147.3660.824.c","article-title":"Molecular Mimicry in Biological Adaptation","volume":"147","author":"Damian","year":"1965","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.4161\/hv.36134","article-title":"Immune camouflage: Relevance to vaccines and human immunology","volume":"10","author":"Moise","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1586\/14760584.2016.1123098","article-title":"T cell epitope redundancy: Cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity","volume":"15","author":"Moise","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/bies.201600083","article-title":"Autoimmunity and the microbiome: T-cell receptor mimicry of \u201cself\u201d and microbial antigens mediates self tolerance in holobionts","volume":"38","year":"2016","journal-title":"BioEssays"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Root-Bernstein, R. (2017). Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102091"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1056\/NEJM196802012780522","article-title":"Package inserts","volume":"278","author":"Bobes","year":"1968","journal-title":"N. Engl. J. Med."},{"key":"ref_29","unstructured":"FDA (2020, June 28). Package Insert. PNEUMOVAX 23 1983, Available online: https:\/\/www.fda.gov\/media\/80547\/download."},{"key":"ref_30","unstructured":"CDC (2020, June 28). About Diphtheria, Tetanus, and Pertussis Vaccines, Available online: https:\/\/www.cdc.gov\/vaccines\/vpd\/dtap-tdap-td\/hcp\/about-vaccine.html."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals","volume":"181","author":"Grifoni","year":"2020","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S.I., Dan, J.M., Burger, Z.C., Rawlings, S.A., Smith, D., and Phillips, E.J. (2020). Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science, eabd3871.","DOI":"10.1126\/science.abd3871"},{"key":"ref_33","first-page":"1","article-title":"Pre-existing immunity to SARS-CoV-2: The knowns and unknowns","volume":"20","author":"Sette","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","first-page":"553","article-title":"Transmission of SARS-CoV-2 by Children","volume":"117","author":"Merckx","year":"2020","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.3201\/eid2608.201142","article-title":"Secondary Transmission of Coronavirus Disease from Presymptomatic Persons, China","volume":"26","author":"Zhang","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/cid\/ciaa201","article-title":"A Well Infant with Coronavirus Disease 2019 with High Viral Load","volume":"71","author":"Kam","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/cid\/ciaa316","article-title":"COVID-19 Transmission Within a Family Cluster by Presymptomatic Carriers in China","volume":"71","author":"Qian","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijid.2020.03.042","article-title":"Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster","volume":"94","author":"Ye","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/1096-9071(200011)62:3<383::AID-JMV11>3.0.CO;2-#","article-title":"Picornavirus proteins share antigenic determinants with heat shock proteins 60\/65","volume":"62","author":"Puolakkainen","year":"2000","journal-title":"J. Med. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1073\/pnas.96.5.2279","article-title":"Crossreactive recognition of viral, self, and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes: Implications for molecular mimicry in autoimmune disease","volume":"96","author":"Misko","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.chom.2014.07.003","article-title":"HIV-1 Envelope gp41 Antibodies Can Originate from Terminal Ileum B Cells that Share Cross-Reactivity with Commensal Bacteria","volume":"16","author":"Trama","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"aab1253","DOI":"10.1126\/science.aab1253","article-title":"Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies","volume":"349","author":"Williams","year":"2015","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2307\/1591261","article-title":"Elimination of Mycoplasmal Plate Agglutination Cross-Reactions in Sera from Chickens Inoculated with Infectious Bursal Disease Viruses","volume":"34","author":"Ross","year":"1990","journal-title":"Avian Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/eji.1830031114","article-title":"L\u2019idiotypie compar\u00e9e des anticorps de lapins diff\u00e9rents contresalmonella abortus-equi et contre le virus de la mosaique du tabac. observation d\u2019une r\u00e9activit\u00e9 crois\u00e9e entre certains idiotypes d\u2019anticorps contre ces deux mat\u00e9riels antig\u00e9niques","volume":"3","author":"Bordenave","year":"1973","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/j.vaccine.2005.01.008","article-title":"Vaccination markers: Designing unique antigens to be added to vaccines to differentiate between natural infection and vaccination","volume":"23","year":"2005","journal-title":"Vaccine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4161\/hv.3.3.4138","article-title":"Positive Vaccination Markers","volume":"3","year":"2007","journal-title":"Hum. Vaccines"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ashford, J.W., Franklin, R., Young, A., Neumann, B., Fernandez, R., Joannides, A., Reyahi, A., and Modis, Y. (2020). Faculty Opinions recommendation of Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: Preliminary evidence that MMR vaccine might provide protection against COVID-19. Fac. Opin. Post Publ. Peer Rev. Biomed. Lit.","DOI":"10.3410\/f.737720584.793574978"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ashford, J.W., Gold, J.E., Tilley, L.P., and Baumgartl, W. (2020). Faculty Opinions recommendation of MMR Vaccine Appears to Confer Strong Protection from COVID-19: Few Deaths from SARS-CoV-2 in Highly Vaccinated Populations. Fac. Opin. Post Publ. Peer Rev. Biomed. Lit.","DOI":"10.3410\/f.737952407.793574976"},{"key":"ref_49","unstructured":"Chumakov, K., and Gallo, R. (2020, April 21). Could an Old Vaccine be a Godsend for New Coronavirus? Using the Oral Polio Vaccine Could Prevent or Reduce the Spread of COVID-19 to Immunized Individuals. USA Today. 21 April 2020. Available online: https:\/\/www.usatoday.com\/story\/opinion\/2020\/04\/21\/oral-polio-vaccine-has-potential-treat-coronavirus-column\/5162859002\/."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2020.04.042","article-title":"Trained Immunity: A Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection","volume":"181","author":"Netea","year":"2020","journal-title":"Cell"},{"key":"ref_51","first-page":"207","article-title":"Stop playing with data: There is no sound evidence that Bacille Calmette-Gu\u00e9rin may avoid SARS-CoV-2 infection (for now)","volume":"91","author":"Gualerzi","year":"2020","journal-title":"Acta Bio Med. Atenei Parm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1001\/jama.2020.8189","article-title":"SARS-CoV-2 Rates in BCG-Vaccinated and Unvaccinated Young Adults","volume":"323","author":"Hamiel","year":"2020","journal-title":"JAMA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-020-01439-4","article-title":"The need for fast-track, high-quality and low-cost studies about the role of the BCG vaccine in the fight against COVID-19","volume":"21","author":"Pereira","year":"2020","journal-title":"Respir. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1128\/iai.55.1.245-252.1987","article-title":"Purification, partial characterization, and identification of a skin-reactive protein antigen of Mycobacterium bovis BCG","volume":"55","author":"Bosmans","year":"1987","journal-title":"Infect. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/clinids\/14.1.313","article-title":"Protein Antigens of Mycobacteria Studied by Quantitative Immunologic Techniques","volume":"14","author":"Harboe","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1128\/iai.61.2.742-750.1993","article-title":"Identification of a Mycobacterium bovis BCG 45\/47-kilodalton antigen complex, an immunodominant target for antibody response after immunization with living bacteria","volume":"61","author":"Romain","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16085","DOI":"10.1038\/ncomms16085","article-title":"Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis","volume":"8","author":"Aguilo","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4566","DOI":"10.1128\/IAI.01660-05","article-title":"Immunogenicity of Mycobacterium tuberculosis Antigens in Mycobacterium bovis BCG-Vaccinated and M. bovis-Infected Cattle","volume":"74","author":"Mustafa","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1086\/591708","article-title":"Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness","volume":"198","author":"Morens","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2324-8955.1000104","article-title":"Prevention of Cervical Cancer in Women: Human Papillomavirus DNA Testing in Atypical Pap Smears","volume":"2","author":"Stefani","year":"2013","journal-title":"J. Virol. Antivir. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cucchiari, D., Peric\u00e0s, J.M., Riera, J., Gumucio, R., Coloma, E., Nicol\u00e1s, D., and Hospital Cl\u00ednic 4H Team (2020). Pneumococcal superinfection in COVID-19 patients: A series of 5 cases. Med. Cl\u00edn.","DOI":"10.1016\/j.medcli.2020.05.022"},{"key":"ref_62","unstructured":"Clancy, C.J., and Nguyen, M.H. (2020). COVID-19, superinfections and antimicrobial development: What can we expect?. Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rawson, T.M., Moore, L.S.P., Zhu, N., Ranganathan, N., Skolimowska, K., Gilchrist, M., Satta, G., Cooke, G., and Holmes, A. (2020). Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing. Clin. Infect. Dis., 530.","DOI":"10.1093\/cid\/ciaa530"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1002\/ppul.24718","article-title":"Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults","volume":"55","author":"Xia","year":"2020","journal-title":"Pediatr. Pulmonol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.jinf.2020.03.019","article-title":"Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up","volume":"80","author":"Wang","year":"2020","journal-title":"J. Infect."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, J.-J., Dong, X., Cao, Y.-Y., Yuan, Y.-D., Yang, Y.-B., Yan, Y.-Q., Akdis, C.A., and Gao, Y. (2020). Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy.","DOI":"10.1111\/all.14238"},{"key":"ref_67","first-page":"438","article-title":"Viral and Bacterial Etiology of Acute Febrile Respiratory Syndrome among Patients in Qinghai, China","volume":"32","author":"Liu","year":"2019","journal-title":"Biomed. Environ. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"198005","DOI":"10.1016\/j.virusres.2020.198005","article-title":"Co-infection with respiratory pathogens among COVID-2019 cases","volume":"285","author":"Zhu","year":"2020","journal-title":"Virus Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s10096-019-03583-2","article-title":"White blood cell count and eosinopenia as valuable tools for the diagnosis of bacterial infections in the ED","volume":"38","author":"Lavoignet","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1007\/s10096-019-03614-y","article-title":"Eosinopenia as a marker of diagnosis and prognostic to distinguish bacterial from aseptic meningitis in pediatrics","volume":"38","author":"Debray","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e00098-19","DOI":"10.1128\/IAI.00098-19","article-title":"Prediction and Validation of Immunogenic Domains of Pneumococcal Proteins Recognized by Human CD4+ T Cells","volume":"87","author":"Poelen","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/S0264-410X(99)00511-3","article-title":"The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection","volume":"18","author":"Briles","year":"2000","journal-title":"Vaccine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1128\/CVI.00395-08","article-title":"Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice","volume":"16","author":"Ferreira","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.ijporl.2014.06.024","article-title":"Pneumococcal PspA and PspC proteins: Potential vaccine candidates for experimental otitis media","volume":"78","author":"Schachern","year":"2014","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lagousi, T., Basdeki, P., Routsias, J.G., and Spoulou, V. (2019). Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens. Vaccines, 7.","DOI":"10.3390\/vaccines7010009"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Masomian, M., Ahmad, Z., Gew, L.T., and Poh, C.L. (2020). Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection. Vaccines, 8.","DOI":"10.3390\/vaccines8010132"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1586\/erv.11.99","article-title":"Pneumococcal polysaccharide vaccination for adults: New perspectives for Europe","volume":"10","author":"Fedson","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"128","DOI":"10.4161\/hv.22550","article-title":"Additive preventive effect of influenza and pneumococcal vaccines in the elderly","volume":"9","author":"Mahamat","year":"2013","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_81","unstructured":"Choi, Y.H., and Miller, E. (2020). Potential impact of Covid-19 response measures on invasive pneumococcal disease in England and Wales. MedRxiv."},{"key":"ref_82","unstructured":"National Institute for Communicable Diseases (South Africa) (2020, July 10). Pneumococcal Conjugate Vaccine Use in the Light of the COVID-19 Pandemic. Available online: https:\/\/www.nicd.ac.za\/diseases-a-z-index\/covid-19\/advice-for-the-public\/pneumococcal-conjugate-vaccine-use-in-the-light-of-the-covid-19-pandemic\/."},{"key":"ref_83","unstructured":"Statens Serum Institut (2020, April 07). Selected Risk Groups are Offered free Pneumococcal Vaccination. Available online: https:\/\/www.sst.dk\/da\/Nyheder\/2020\/Udvalgte-risikogrupper-faar-tilbud-om-gratis-vaccination-mod-pneumokokker."},{"key":"ref_84","unstructured":"(2020, August 19). New Zealand. Policy on Pneumococcal Vaccination and COVID. Available online: https:\/\/www.nzdoctor.co.nz\/article\/news\/pneumococcal-vax-potential-option-improve-outcomes-compromised-patients-face-covid-19."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/559\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:13:14Z","timestamp":1760177594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/4\/559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":84,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["vaccines8040559"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8040559","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,24]]}}}