{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:32:11Z","timestamp":1772253131183,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T00:00:00Z","timestamp":1546473600000},"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>Since the introduction of the 13-valent pneumococcal conjugate vaccine, a number of studies have demonstrated the limited efficacy of the pneumococcal serotype 3 component of this vaccine. Evidence from seven countries (Denmark, France, Greece, Portugal, Sweden, UK, US) shows limited or no effectiveness of the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal disease and carriage. The serotype 3 capsule has some unique characteristics that may serve to explain this lack of efficacy\u2014capsular polysaccharide is abundantly expressed, leading to a greater thickness of capsule, and free capsular polysaccharide may be released during growth. The serotype 3 component of the Luminex multiplex assay demonstrates inferior inter-laboratory reproducibility than other components and results may not be reliable. This communication outlines this evidence and discusses whether it is necessary to include serotype 3 in the assay in the future.<\/jats:p>","DOI":"10.3390\/vaccines7010004","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T11:11:56Z","timestamp":1546513916000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Should Pneumococcal Serotype 3 Be Included in Serotype-Specific Immunoassays?"],"prefix":"10.3390","volume":"7","author":[{"given":"Ezra","family":"Linley","sequence":"first","affiliation":[{"name":"Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Bell","sequence":"additional","affiliation":[{"name":"Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna F.","family":"Gritzfeld","sequence":"additional","affiliation":[{"name":"UK Experimental Arthritis Treatment Centre for Children, Department of Women\u2019s and Children\u2019s Health, Institute of Translational Medicine (Child Health), University of Liverpool, Institute in the Park, Alder Hey Children\u2019s NHS Foundation Trust Hospital, Eaton Road, Liverpool L12 2AP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Borrow","sequence":"additional","affiliation":[{"name":"Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S1473-3099(18)30399-2","article-title":"The Changing Epidemiology of Pneumococcal Diseases","volume":"18","author":"Hulten","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Balsells, E., Guillot, L., Nair, H., and Kyaw, M.H. (2017). Serotype Distribution of Streptococcus Pneumoniae Causing Invasive Disease in Children in the Post-PCV Era: A Systematic Review and Meta-Analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177113"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s10096-014-2062-6","article-title":"Pneumococcal Empyema and Complicated Pneumonias: Global Trends in Incidence, Prevalence, and Serotype Epidemiology","volume":"33","author":"Fletcher","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alonso, M., Marimon, J.M., Ercibengoa, M., P\u00e9rez-Yarza, E.G., and P\u00e9rez-Trallero, E. (2013). Dynamics of Streptococcus Pneumoniae Serotypes Causing Acute Otitis Media Isolated from Children with Spontaneous Middle-Ear Drainage over a 12-Year Period (1999\u20132010) in a Region of Northern Spain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054333"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1086\/313608","article-title":"Which Pneumococcal Serogroups Cause the Most Invasive Disease: Implications for Conjugate Vaccine Formulation and Use, Part I","volume":"30","author":"Hausdorff","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1128\/CVI.00735-14","article-title":"Use and Clinical Interpretation of Pneumococcal Antibody Measurements in the Evaluation of Humoral Immune Function","volume":"22","author":"Daly","year":"2015","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1309\/LMCH-C4Q2-VFL9-3T1A","article-title":"A Multiplexed Fluorescent Microsphere Immunoassay for Antibodies to Pneumococcal Capsular Polysaccharides","volume":"117","author":"Pickering","year":"2002","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00198","DOI":"10.1016\/j.heliyon.2016.e00198","article-title":"The Incidence of Invasive Pneumococcal Serotype 3 Disease in the Danish Population Is Not Reduced by PCV-13 Vaccination","volume":"2","author":"Slotved","year":"2016","journal-title":"Heliyon"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hor\u00e1cio, A.N., Silva-Costa, C., Lopes, J.P., Ramirez, M., Melo-Cristino, J., and Vaz, T. (2016). The Portuguese Group for the Study of Streptococcal Infections. Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012\u20132014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01616"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.3201\/eid2407.180029","article-title":"Pediatric Complicated Pneumonia Caused by Streptococcus Pneumoniae Serotype 3 in 13-Valent Pneumococcal Conjugate Vaccinees, Portugal, 2010\u20132015","volume":"24","author":"Brito","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S1473-3099(14)71081-3","article-title":"Effect of Use of 13-Valent Pneumococcal Conjugate Vaccine in Children on Invasive Pneumococcal Disease in Children and Adults in the USA: Analysis of Multisite, Population-Based Surveillance","volume":"15","author":"Moore","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S1473-3099(14)70822-9","article-title":"Serotype-Specific Effectiveness and Correlates of Protection for the 13-Valent Pneumococcal Conjugate Vaccine: A Postlicensure Indirect Cohort Study","volume":"14","author":"Andrews","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1093\/cid\/cix418","article-title":"Characteristics and Serotype Distribution of Childhood Cases of Invasive Pneumococcal Disease Following Pneumococcal Conjugate Vaccination in England and Wales, 2006\u20132014","volume":"65","author":"Oligbu","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1183\/13993003.01451-2015","article-title":"Effects of PCV7 and PCV13 on Invasive Pneumococcal Disease and Carriage in Stockholm, Sweden","volume":"47","author":"Galanis","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez, \u00c1., Ciruela, P., Hern\u00e1ndez, S., Garc\u00eda-Garc\u00eda, J.J., Soldevila, N., Izquierdo, C., Moraga-Llop, F., D\u00edaz, A., de Sevilla, M.F., and Gonz\u00e1lez-Peris, S. (2017). Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine in Preventing Invasive Pneumococcal Disease in Children Aged 7\u201359 Months. A Matched Case-Control Study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183191"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/INF.0b013e318247ef84","article-title":"Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal nasopharyngeal carriage in children with acute otitis media","volume":"31","author":"Cohen","year":"2012","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1016\/j.vaccine.2015.08.010","article-title":"A 13-Year Survey of Pneumococcal Nasopharyngeal Carriage in Children with Acute Otitis Media Following PCV7 and PCV13 Implementation","volume":"33","author":"Cohen","year":"2015","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/cid\/cit428","article-title":"Comparative Immunogenicity and Efficacy of 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines in Reducing Nasopharyngeal Colonization: A Randomized Double-Blind Trial","volume":"57","author":"Dagan","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/S0140-6736(06)68304-9","article-title":"Pneumococcal Capsular Polysaccharides Conjugated to Protein D for Prevention of Acute Otitis Media Caused by Both Streptococcus Pneumoniae and Non-Typable Haemophilus Influenzae: A Randomised Double-Blind Efficacy Study","volume":"367","author":"Prymula","year":"2006","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6802","DOI":"10.1016\/j.vaccine.2012.09.019","article-title":"Impact and Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine against Invasive Pneumococcal Disease in the Elderly in England and Wales","volume":"30","author":"Andrews","year":"2012","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S2213-2600(16)00052-7","article-title":"Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: A matched case-control study","volume":"4","author":"Moore","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Van der Linden, M., Falkenhorst, G., Perniciaro, S., Fitzner, C., and Im\u00f6hl, M. (2016). Effectiveness of Pneumococcal Conjugate Vaccines (PCV7 and PCV13) against Invasive Pneumococcal Disease among Children under Two Years of Age in Germany. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161257"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1016\/j.vaccine.2018.07.069","article-title":"Commentary on paradoxical observations pertaining to the impact of the 13-valent pneumococcal conjugate vaccine on serotype 3 Streptococcus pneumoniae infections in children","volume":"36","year":"2018","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1016\/j.vaccine.2015.04.005","article-title":"Effectiveness of Three Pneumococcal Conjugate Vaccines to Prevent Invasive Pneumococcal Disease in Quebec, Canada","volume":"33","author":"Deceuninck","year":"2015","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9675","DOI":"10.1016\/j.vaccine.2011.10.012","article-title":"Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) when given as a toddler dose to children immunized with PCV7 as infants","volume":"29","author":"Grimprel","year":"2011","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5186","DOI":"10.1016\/j.vaccine.2017.07.103","article-title":"Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia","volume":"35","author":"Urbancikova","year":"2017","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/cid\/cix673","article-title":"Pan-serotype Reduction in Progression of Streptococcus pneumoniae to Otitis Media After Rollout of Pneumococcal Conjugate Vaccines","volume":"65","author":"Lewnard","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/cid\/ciw347","article-title":"Impact of Widespread Introduction of Pneumococcal Conjugate Vaccines on Pneumococcal and Nonpneumococcal Otitis Media","volume":"63","author":"Leibovitz","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1016\/j.vaccine.2009.03.017","article-title":"Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics","volume":"27","author":"Poolman","year":"2009","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1128\/IAI.67.5.2327-2333.1999","article-title":"Relationship between Cell Surface Carbohydrates and Intrastrain Variation on Opsonophagocytosis of Streptococcus pneumoniae","volume":"67","author":"Kim","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1128\/CVI.00591-15","article-title":"Capsular Polysaccharide (CPS) Release by Serotype 3 Pneumococcal Strains Reduces the Protective Effect of Anti-Type 3 CPS Antibodies","volume":"23","author":"Choi","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1097\/01.inf.0000143640.03214.18","article-title":"Immunogenicity and Safety of the Eleven Valent Pneumococcal Polysaccharide-Protein D Conjugate Vaccine in Infants","volume":"23","author":"Nurkka","year":"2004","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1586\/erv.11.8","article-title":"Hyporesponsiveness and Its Clinical Implications after Vaccination with Polysaccharide or Glycoconjugate Vaccines","volume":"10","author":"Poolman","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_34","unstructured":"(2018, December 06). UK NEQAS Immunology, Immunochemistry and Allergy. Available online: https:\/\/www.immqas.org.uk."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/1\/4\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:23:25Z","timestamp":1760185405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/1\/4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,3]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["vaccines7010004"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7010004","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734891274.793573938","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,3]]}}}