{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T01:46:42Z","timestamp":1779328002202,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/09427-5"],"award-info":[{"award-number":["2016\/09427-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303198\/2014-1"],"award-info":[{"award-number":["303198\/2014-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["130505\/2018-8"],"award-info":[{"award-number":["130505\/2018-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Widespread use of pneumococcal conjugate vaccines (PCVs) has led to substitution of vaccine-type (VT) strains by non-vaccine type (NVT) strains in nasopharyngeal carriage. We compared the efficacy of PCV13 and a nasal protein formulation containing pneumococcal surface protein A (PspA) adjuvanted with the whole-cell pertussis vaccine (wP) in the protection against co-colonization challenge models in mice with VT and NVT strains expressing different PspAs. Immunized mice were challenged with two different mixtures: i. VT4 (PspA3) + NVT33 (PspA1) and ii. VT23F (PspA2) + NVT15B\/C (PspA4). Results from the first mixture showed a reduction in loads of VT4 strain in the nasopharynx of mice immunized with PCV13. A statistical difference between the loads of the VT and NVT strains was observed, indicating a competitive advantage for the NVT strain in PCV13-immunized animals. In the second mixture, no reduction was observed for the VT23F strain, probably due to low levels of anti-23F polysaccharide IgG induced by PCV13. Interestingly, a combination of the PspA formulation containing wP with PCV13 led to a reduction in colonization with both strains of the two mixtures tested, similar to the groups immunized nasally with wP or PspA plus wP. These results indicate that a combination of vaccines may be a useful strategy to overcome pneumococcal serotype replacement.<\/jats:p>","DOI":"10.3390\/pathogens9040278","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T04:45:31Z","timestamp":1586753131000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Gabriela B. C.","family":"Colichio","sequence":"first","affiliation":[{"name":"Laboratorio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1661-3525","authenticated-orcid":false,"given":"Giuliana S.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratorio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1481-0691","authenticated-orcid":false,"given":"Tasson C.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratorio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Leonor S.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratorio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliane N.","family":"Miyaji","sequence":"additional","affiliation":[{"name":"Laboratorio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adegbola, R.A., DeAntonio, R., Hill, P.C., Roca, A., Usuf, E., Hoet, B., and Greenwood, B.M. (2014). Carriage of Streptococcus pneumoniae and other respiratory bacterial pathogens in low and lower-middle income countries: A systematic review and meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103293"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wyllie, A.L., Chu, M.L., Schellens, M.H., Van Engelsdorp Gastelaars, J., Jansen, M.D., van der Ende, A., Bogaert, D., Sanders, E.A., and Trzcinski, K. (2014). Streptococcus pneumoniae in saliva of Dutch primary school children. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102045"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1128\/JCM.00157-11","article-title":"Improved detection of nasopharyngeal cocolonization by multiple pneumococcal serotypes by use of latex agglutination or molecular serotyping by microarray","volume":"49","author":"Turner","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e744","DOI":"10.1016\/S2214-109X(18)30247-X","article-title":"Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccinges: Global, regional, and national estimates for 2000-15","volume":"6","author":"Wahl","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1128\/CMR.00024-15","article-title":"Pneumococcal Capsules and Their Types: Past, Present, and Future","volume":"28","author":"Geno","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/01.inf.0000154326.77617.3e","article-title":"Effect of the seven-valent conjugate pneumococcal vaccine on carriage and drug resistance of Streptococcus pneumoniae in healthy children attending day-care centers in Lisbon","volume":"24","author":"Frazao","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e408","DOI":"10.1542\/peds.2004-2338","article-title":"Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004","volume":"116","author":"Huang","year":"2005","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/21645515.2015.1118593","article-title":"Interim results of an ecological experiment\u2014Conjugate vaccination against the pneumococcus and serotype replacement","volume":"12","author":"Hausdorff","year":"2016","journal-title":"Human Vaccines Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1128\/IAI.68.2.796-800.2000","article-title":"Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae","volume":"68","author":"Briles","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1128\/IAI.68.5.3028-3033.2000","article-title":"Immunization of mice with combinations of pneumococcal virulence proteins elicits enhanced protection against challenge with Streptococcus pneumoniae","volume":"68","author":"Ogunniyi","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1086\/376571","article-title":"Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae","volume":"188","author":"Briles","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5889","DOI":"10.1128\/IAI.68.10.5889-5900.2000","article-title":"Diversity of PspA: Mosaic genes and evidence for past recombination in Streptococcus pneumoniae","volume":"68","author":"Hollingshead","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/S0264-410X(99)00530-7","article-title":"Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules","volume":"18","author":"Nabors","year":"2000","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1128\/CVI.00430-09","article-title":"Immunization of mice with single PspA fragments induces antibodies capable of mediating complement deposition on different pneumococcal strains and cross-protection","volume":"17","author":"Moreno","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.1016\/S0264-410X(00)00285-1","article-title":"The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae","volume":"19","author":"Briles","year":"2000","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1016\/S0264-410X(00)00046-3","article-title":"Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model","volume":"18","author":"Lipsitch","year":"2000","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00902","DOI":"10.1128\/mBio.00902-15","article-title":"Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model","volume":"6","author":"Trzcinski","year":"2015","journal-title":"MBio"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tostes, R.O., Rodrigues, T.C., da Silva, J.B., Schanoski, A.S., Oliveira, M.L., and Miyaji, E.N. (2017). Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170157"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1128\/IAI.69.12.7481-7486.2001","article-title":"Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans","volume":"69","author":"Johansson","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/mi.2013.41","article-title":"Pneumococcal IgA1 protease subverts specific protection by human IgA1","volume":"7","author":"Janoff","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kono, M., Zafar, M.A., Zuniga, M., Roche, A.M., Hamaguchi, S., and Weiser, J.N. (2016). Single Cell Bottlenecks in the Pathogenesis of Streptococcus pneumoniae. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005887"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20140342","DOI":"10.1098\/rstb.2014.0342","article-title":"Carriage burden, multiple colonization and antibiotic pressure promote emergence of resistant vaccine escape pneumococci","volume":"370","author":"Mitchell","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Oliveira, M.L., Miyaji, E.N., Ferreira, D.M., Moreno, A.T., Ferreira, P.C., Lima, F.A., Santos, F.L., Sakauchi, M.A., Takata, C.S., and Higashi, H.G. (2010). Combination of pneumococcal surface protein A (PspA) with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010863"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1128\/IAI.72.7.4290-4292.2004","article-title":"Multiserotype protection of mice against pneumococcal colonization of the nasopharynx and middle ear by killed nonencapsulated cells given intranasally with a nontoxic adjuvant","volume":"72","author":"Malley","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kuipers, K., Diavatopoulos, D.A., van Opzeeland, F., Simonetti, E., van den Kieboom, C.H., Kerstholt, M., Borczyk, M., van IngenSchenau, D., Brandsma, E.T., and Netea, M.G. (2016). Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiw160"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/mi.2016.71","article-title":"Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage","volume":"10","author":"Mitsi","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/mi.2014.55","article-title":"Antibody blocks acquisition of bacterial colonization through agglutination","volume":"8","author":"Roche","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lu, Y.J., Gross, J., Bogaert, D., Finn, A., Bagrade, L., Zhang, Q., Kolls, J.K., Srivastava, A., Lundgren, A., and Forte, S. (2008). Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000159"},{"key":"ref_29","first-page":"1899","article-title":"Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice","volume":"119","author":"Zhang","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/s41590-018-0231-y","article-title":"Inflammation induced by influenza virus impairs human innate immune control of pneumococcus","volume":"19","author":"Jochems","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1172\/JCI128865","article-title":"Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization","volume":"130","author":"Jochems","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1128\/IAI.72.1.114-122.2004","article-title":"Effects of PspA and antibodies to PspA on activation and deposition of complement on the pneumococcal surface","volume":"72","author":"Ren","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Habets, M.N., van Selm, S., van der Gaast-de Jongh, C.E., Diavatopoulos, D.A., and de Jonge, M.I. (2017). A novel flow cytometry-based assay for the quantification of antibody-dependent pneumococcal agglutination. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170884"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1093\/cid\/ciy726","article-title":"Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia","volume":"68","author":"Usuf","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Marks, L.R., Reddinger, R.M., and Hakansson, A.P. (2012). High levels of genetic recombination during nasopharyngeal carriage and biofilm formation in Streptococcus pneumoniae. MBio, 3.","DOI":"10.1128\/mBio.00200-12"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1128\/JCM.44.1.124-131.2006","article-title":"Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates","volume":"44","author":"Pai","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0022-1759(90)90029-U","article-title":"Removal of endotoxin from protein solutions by phase separation using Triton X-114","volume":"132","author":"Aida","year":"1990","journal-title":"J. Immunol. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Teodorowicz, M., Perdijk, O., Verhoek, I., Govers, C., Savelkoul, H.F., Tang, Y., Wichers, H., and Broersen, K. (2017). Optimized Triton X-114 assisted lipopolysaccharide (LPS) removal method reveals the immunomodulatory effect of food proteins. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173778"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.vaccine.2016.12.055","article-title":"Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain","volume":"35","author":"Indrawati","year":"2017","journal-title":"Vaccine"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/4\/278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:17:33Z","timestamp":1760174253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/4\/278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,10]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["pathogens9040278"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9040278","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,10]]}}}