{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T09:44:59Z","timestamp":1775900699264,"version":"3.50.1"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordenadoria de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Microbiol Immunol"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s00430-025-00848-w","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:14:08Z","timestamp":1756462448000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and efficacy of an intramuscular bivalent vaccine against influenza and Streptococcus pneumoniae infections in mice"],"prefix":"10.1007","volume":"214","author":[{"given":"Kimberly Freitas","family":"Cardoso","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara Regina Alves","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora Silva","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Senra \u00c1lvares","family":"da Silva Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketyllen Reis Andrade","family":"de Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Giarola","family":"da Silva Messias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"de Faria Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rayanne Rosa","family":"Do Nascimento Mac\u00e1rio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyse Julia Ferreira","family":"de Jesus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Luiza Pessoa","family":"De Mendon\u00e7a \u00c2ngelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"de Paula Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e2mick Layene Moreira","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora Satiko","family":"Kano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro Augusto","family":"Alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo Antonio Pascoal","family":"Xavier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olindo Assis","family":"Martins-Filho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remo Castro","family":"Russo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Tostes","family":"Gazzinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliane Namie","family":"Miyaji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiana Couto","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"de Magalh\u00e3es Vieira Machado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcio Sobreira Silva","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"848_CR1","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/S0140-6736(17)30129-0","volume":"390","author":"C Paules","year":"2017","unstructured":"Paules C, Subbarao K (2017) Influenza. Lancet 390:697\u2013708","journal-title":"Lancet"},{"key":"848_CR2","doi-asserted-by":"publisher","first-page":"4713","DOI":"10.1016\/j.vaccine.2014.02.014","volume":"32","author":"IG Barr","year":"2014","unstructured":"Barr IG et al (2014) WHO recommendations for the viruses used in the 2013\u20132014 Northern hemisphere influenza vaccine: epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013. Vaccine 32:4713\u20134725","journal-title":"Vaccine"},{"key":"848_CR3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrmicro.2017.118","volume":"16","author":"VN Petrova","year":"2018","unstructured":"Petrova VN, Russell CA (2018) The evolution of seasonal influenza viruses. Nat Rev Microbiol 16:47\u201360","journal-title":"Nat Rev Microbiol"},{"key":"848_CR4","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/infdis\/jix074","volume":"215","author":"DM Skowronski","year":"2017","unstructured":"Skowronski DM et al (2017) Serial vaccination and the antigenic distance hypothesis: effects on influenza vaccine effectiveness during A(H3N2) epidemics in canada, 2010\u20132011 to 2014\u20132015. J Infect Dis 215:1059\u20131099","journal-title":"J Infect Dis"},{"key":"848_CR5","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.3389\/fmicb.2017.01041","volume":"8","author":"DE Morris","year":"2017","unstructured":"Morris DE, Cleary DW, Clarke SC (2017) Secondary bacterial infections associated with influenza pandemics. Front Microbiol 8:1041","journal-title":"Front Microbiol"},{"key":"848_CR6","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1111\/irv.12089","volume":"7","author":"C Joseph","year":"2013","unstructured":"Joseph C, Togawa Y, Shindo N (2013) Bacterial and viral infections associated with influenza. Influenza Other Respir Viruses 7:105\u2013113","journal-title":"Influenza Other Respir Viruses"},{"key":"848_CR7","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1128\/CMR.00058-05","volume":"19","author":"JA McCullers","year":"2006","unstructured":"McCullers JA (2006) Insights into the interaction between influenza virus and Pneumococcus. Clin Microbiol Rev 19:571\u2013582","journal-title":"Clin Microbiol Rev"},{"key":"848_CR8","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.3201\/eid1408.071313","volume":"14","author":"JF Brundage","year":"2008","unstructured":"Brundage JF, Shanks GD (2008) Deaths from bacterial pneumonia during 1918-19 influenza pandemic. Emerg Infect Dis 14:1193\u20131199","journal-title":"Emerg Infect Dis"},{"key":"848_CR9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.5858\/134.2.235","volume":"134","author":"JR Gill","year":"2010","unstructured":"Gill JR et al (2010) Pulmonary pathologic findings of fatal 2009 pandemic influenza A\/H1N1 viral infections. Arch Pathol Lab Med 134:235\u2013243","journal-title":"Arch Pathol Lab Med"},{"key":"848_CR10","doi-asserted-by":"publisher","first-page":"e00937","DOI":"10.1128\/mBio.00937-20","volume":"11","author":"F Ganaie","year":"2020","unstructured":"Ganaie F et al (2020) A new Pneumococcal capsule type, 10D, is the 100th serotype and has a large Cps fragment from an oral Streptococcus. mBio 11:e00937\u2013e00920","journal-title":"mBio"},{"key":"848_CR11","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1080\/17476348.2019.1562339","volume":"13","author":"P Peyrani","year":"2019","unstructured":"Peyrani P, Mandell L, Torres A, Tillotson GS (2019) The burden of community-acquired bacterial pneumonia in the era of antibiotic resistance. Expert Rev Respir Med 13:139\u2013152","journal-title":"Expert Rev Respir Med"},{"key":"848_CR12","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.3389\/fimmu.2018.01366","volume":"9","author":"LRK Brooks","year":"2018","unstructured":"Brooks LRK, Mias GI (2018) Streptococcus pneumoniae\u2019s virulence and host immunity: aging, diagnostics, and prevention. Front Immunol 9:1366","journal-title":"Front Immunol"},{"key":"848_CR13","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/S1473-3099(04)00938-7","volume":"4","author":"D Bogaert","year":"2004","unstructured":"Bogaert D, de Groot R, Hermans PW (2004) M. Streptococcus pneumoniae colonisation: the key to Pneumococcal disease. Lancet Infect Dis 4:144\u2013154","journal-title":"Lancet Infect Dis"},{"key":"848_CR14","doi-asserted-by":"publisher","first-page":"e744","DOI":"10.1016\/S2214-109X(18)30247-X","volume":"6","author":"B Wahl","year":"2018","unstructured":"Wahl B et al (2018) Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000 \u00d7 2013. Lancet Glob Health 6:e744\u2013e757","journal-title":"Lancet Glob Health"},{"key":"848_CR15","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1080\/21645515.2015.1118593","volume":"12","author":"WP Hausdorff","year":"2016","unstructured":"Hausdorff WP, Hanage WP (2016) Interim results of an ecological experiment\u2014conjugate vaccination against the Pneumococcus and serotype replacement. Hum Vaccin Immunother 12:358\u2013374","journal-title":"Hum Vaccin Immunother"},{"key":"848_CR16","doi-asserted-by":"publisher","first-page":"5628","DOI":"10.1080\/21645515.2021.1985353","volume":"17","author":"Q Du","year":"2021","unstructured":"Du Q, Shi W, Yu D, Yao K (2021) Epidemiology of non-vaccine serotypes of Streptococcus pneumoniae before and after universal administration of Pneumococcal conjugate vaccines. Hum Vaccin Immunother 17:5628\u20135637","journal-title":"Hum Vaccin Immunother"},{"key":"848_CR17","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1056\/NEJMoa1408544","volume":"372","author":"MJM Bonten","year":"2015","unstructured":"Bonten MJM et al (2015) Polysaccharide conjugate vaccine against Pneumococcal pneumonia in adults. N Engl J Med 372:1114\u20131125","journal-title":"N Engl J Med"},{"key":"848_CR18","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.1016\/j.vaccine.2018.04.010","volume":"36","author":"M-CC Brandileone","year":"2018","unstructured":"Brandileone M-CC, Almeida SCG, Minamisava R, Andrade A-L (2018) Distribution of invasive Streptococcus pneumoniae serotypes before and 5 years after the introduction of 10-valent Pneumococcal conjugate vaccine in Brazil. Vaccine 36:2559\u20132566","journal-title":"Vaccine"},{"key":"848_CR19","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1016\/S0140-6736(10)62225-8","volume":"378","author":"DM Weinberger","year":"2011","unstructured":"Weinberger DM, Malley R, Lipsitch M (2011) Serotype replacement in disease after Pneumococcal vaccination. Lancet 378:1962\u20131973","journal-title":"Lancet"},{"key":"848_CR20","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1097\/INF.0b013e31824de9f6","volume":"31","author":"SP Fitzwater","year":"2012","unstructured":"Fitzwater SP, Chandran A, Santosham M, Johnson HL (2012) The worldwide impact of the seven-valent Pneumococcal conjugate vaccine. Pediatr Infect Dis J 31:501","journal-title":"Pediatr Infect Dis J"},{"key":"848_CR21","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1186\/s12889-022-14051-6","volume":"22","author":"T Hu","year":"2022","unstructured":"Hu T et al (2022) Incidence of invasive Pneumococcal disease in children with commercial insurance or medicaid coverage in the united States before and after the introduction of 7- and 13-valent Pneumococcal conjugate vaccines during 1998\u20132018. BMC Public Health 22:1677","journal-title":"BMC Public Health"},{"key":"848_CR22","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1080\/21645515.2015.1087625","volume":"12","author":"K Moffitt","year":"2016","unstructured":"Moffitt K, Malley R (2016) Rationale and prospects for novel Pneumococcal vaccines. Hum Vaccin Immunother 12:383\u2013392","journal-title":"Hum Vaccin Immunother"},{"key":"848_CR23","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","volume":"399","author":"CJL Murray","year":"2022","unstructured":"Murray CJL et al (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399:629\u2013655","journal-title":"Lancet"},{"key":"848_CR24","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1016\/j.vaccine.2016.12.037","volume":"35","author":"JE Cornick","year":"2017","unstructured":"Cornick JE et al (2017) The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1. Vaccine 35, 972\u2013980","journal-title":"Vaccine"},{"key":"848_CR25","doi-asserted-by":"publisher","first-page":"3293","DOI":"10.1128\/iai.58.10.3293-3299.1990","volume":"58","author":"MJ Crain","year":"1990","unstructured":"Crain MJ et al (1990) Pneumococcal surface protein A (PspA) is serologically highly variable and is expressed by all clinically important capsular serotypes of Streptococcus pneumoniae. Infect Immun 58:3293\u20133299","journal-title":"Infect Immun"},{"key":"848_CR26","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1128\/IAI.71.1.75-85.2003","volume":"71","author":"B Ren","year":"2003","unstructured":"Ren B, Szalai AJ, Thomas O, Hollingshead SK, Briles DE (2003) Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Infect Immun 71:75\u201385","journal-title":"Infect Immun"},{"key":"848_CR27","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1128\/CVI.00393-12","volume":"19","author":"B Ren","year":"2012","unstructured":"Ren B, Li J, Genschmer K, Hollingshead SK, Briles DE (2012) The absence of PspA or presence of antibody to PspA facilitates the complement-dependent phagocytosis of Pneumococci in vitro. Clin Vaccine Immunol 19:1574\u20131582","journal-title":"Clin Vaccine Immunol"},{"key":"848_CR28","doi-asserted-by":"publisher","first-page":"5877","DOI":"10.1128\/IAI.00839-07","volume":"75","author":"J Li","year":"2007","unstructured":"Li J, Glover DT, Szalai AJ, Hollingshead SK, Briles DE (2007) PspA and PspC minimize immune adherence and transfer of Pneumococci from erythrocytes to macrophages through their effects on complement activation. Infect Immun 75:5877\u20135885","journal-title":"Infect Immun"},{"key":"848_CR29","doi-asserted-by":"publisher","first-page":"5327","DOI":"10.4049\/jimmunol.1201967","volume":"189","author":"R Mukerji","year":"2012","unstructured":"Mukerji R et al (2012) Pneumococcal surface protein A inhibits complement deposition on the Pneumococcal surface by competing with the binding of C-reactive protein to cell-surface phosphocholine. J Immunol 189:5327\u20135335","journal-title":"J Immunol"},{"key":"848_CR30","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1128\/IAI.72.1.114-122.2004","volume":"72","author":"B Ren","year":"2004","unstructured":"Ren B, Szalai AJ, Hollingshead SK, Briles DE (2004) Effects of PspA and antibodies to PspA on activation and deposition of complement on the Pneumococcal surface. Infect Immun 72:114\u2013122","journal-title":"Infect Immun"},{"key":"848_CR31","doi-asserted-by":"publisher","first-page":"826264","DOI":"10.3389\/fcimb.2022.826264","volume":"12","author":"JR Lane","year":"2022","unstructured":"Lane JR, Tata M, Briles DE, Orihuela CJ (2022) A Jack of all trades: the role of Pneumococcal surface protein A in the pathogenesis of Streptococcus pneumoniae. Front Cell Infect Microbiol 12:826264","journal-title":"Front Cell Infect Microbiol"},{"key":"848_CR32","doi-asserted-by":"publisher","first-page":"109267","DOI":"10.1016\/j.celrep.2021.109267","volume":"35","author":"S-S Park","year":"2021","unstructured":"Park S-S et al (2021) Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza. Cell Rep 35:109267","journal-title":"Cell Rep"},{"key":"848_CR33","doi-asserted-by":"publisher","first-page":"e00673","DOI":"10.1128\/mBio.00673-21","volume":"12","author":"S-S Park","year":"2021","unstructured":"Park S-S et al (2021) Streptococcus pneumoniae binds to host lactate dehydrogenase via PspA and PspC to enhance virulence. mBio 12:e00673\u2013e00621","journal-title":"mBio"},{"key":"848_CR34","doi-asserted-by":"publisher","first-page":"5889","DOI":"10.1128\/IAI.68.10.5889-5900.2000","volume":"68","author":"SK Hollingshead","year":"2000","unstructured":"Hollingshead SK, Becker R, Briles DE (2000) Diversity of pspa: mosaic genes and evidence for past recombination in Streptococcus pneumoniae. Infect Immun 68:5889\u20135900","journal-title":"Infect Immun"},{"key":"848_CR35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2147\/IDR.S286187","volume":"14","author":"H Jiang","year":"2021","unstructured":"Jiang H et al (2021) PspA diversity, serotype distribution and antimicrobial resistance of invasive Pneumococcal isolates from paediatric patients in shenzhen, China. Infect Drug Resist 14:49\u201358","journal-title":"Infect Drug Resist"},{"key":"848_CR36","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1128\/CVI.00177-08","volume":"15","author":"MM Melin","year":"2008","unstructured":"Melin MM et al (2008) Distribution of Pneumococcal surface protein A families 1 and 2 among Streptococcus pneumoniae isolates from children in Finland who had acute otitis media or were nasopharyngeal carriers. Clin Vaccine Immunol 15:1555\u20131563","journal-title":"Clin Vaccine Immunol"},{"key":"848_CR37","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1099\/jmm.0.46268-0","volume":"55","author":"SK Hollingshead","year":"2006","unstructured":"Hollingshead SK et al (2006) Pneumococcal surface protein A (PspA) family distribution among clinical isolates from adults over 50 years of age collected in seven countries. J Med Microbiol 55:215\u2013221","journal-title":"J Med Microbiol"},{"key":"848_CR38","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1099\/jmm.0.000775","volume":"67","author":"M Kawaguchiya","year":"2018","unstructured":"Kawaguchiya M et al (2018) Genetic diversity of Pneumococcal surface protein A (PspA) in paediatric isolates of non-conjugate vaccine serotypes in Japan. J Med Microbiol 67:1130\u20131138","journal-title":"J Med Microbiol"},{"key":"848_CR39","doi-asserted-by":"publisher","first-page":"617573","DOI":"10.3389\/fcimb.2021.617573","volume":"11","author":"B Chang","year":"2021","unstructured":"Chang B et al (2021) Distribution and variation of serotypes and Pneumococcal surface protein A clades of Streptococcus pneumoniae strains isolated from adult patients with invasive Pneumococcal disease in Japan. Front Cell Infect Microbiol 11:617573","journal-title":"Front Cell Infect Microbiol"},{"key":"848_CR40","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1086\/513980","volume":"175","author":"H-Y Wu","year":"1997","unstructured":"Wu H-Y, Nahm MH, Guo Y, Russell MW, Briles DE (1997) Intranasal immunization of mice with PspA (Pneumococcal surface protein A) can prevent intranasal carriage, pulmonary infection, and sepsis with Streptococcus pneumoniae. J Infect Dis 175:839\u2013846","journal-title":"J Infect Dis"},{"key":"848_CR41","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1016\/S0264-410X(99)00530-7","volume":"18","author":"GS Nabors","year":"2000","unstructured":"Nabors GS et al (2000) Immunization of healthy adults with a single Recombinant Pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules. Vaccine 18:1743\u20131754","journal-title":"Vaccine"},{"key":"848_CR42","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1016\/j.vaccine.2010.12.117","volume":"29","author":"H Ezoe","year":"2011","unstructured":"Ezoe H et al (2011) Intranasal vaccination with Pneumococcal surface protein A plus poly(I:C) protects against secondary Pneumococcal pneumonia in mice. Vaccine 29:1754\u20131761","journal-title":"Vaccine"},{"key":"848_CR43","doi-asserted-by":"publisher","first-page":"5607","DOI":"10.1016\/j.vaccine.2014.07.108","volume":"32","author":"Z Piao","year":"2014","unstructured":"Piao Z et al (2014) Protective properties of a fusion Pneumococcal surface protein A (PspA) vaccine against Pneumococcal challenge by five different PspA clades in mice. Vaccine 32:5607\u20135613","journal-title":"Vaccine"},{"key":"848_CR44","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1086\/600871","volume":"200","author":"QO King","year":"2009","unstructured":"King QO, Lei B, Harmsen AG (2009) Pneumococcal surface protein A contributes to secondary Streptococcus pneumoniae infection after influenza virus infection. J Infect Dis 200:537\u2013545","journal-title":"J Infect Dis"},{"key":"848_CR45","doi-asserted-by":"publisher","first-page":"6834","DOI":"10.1016\/j.vaccine.2018.08.045","volume":"36","author":"R Mukerji","year":"2018","unstructured":"Mukerji R et al (2018) The diversity of the proline-rich domain of Pneumococcal surface protein A (PspA): potential relevance to a broad-spectrum vaccine. Vaccine 36:6834\u20136843","journal-title":"Vaccine"},{"key":"848_CR46","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3390\/vaccines9030209","volume":"9","author":"NR Scott","year":"2021","unstructured":"Scott NR, Mann B, Tuomanen EI, Orihuela CJ (2021) Multi-valent protein hybrid Pneumococcal vaccines: a strategy for the next generation of vaccines. Vaccines (Basel) 9:209","journal-title":"Vaccines (Basel)"},{"key":"848_CR47","doi-asserted-by":"publisher","first-page":"23517","DOI":"10.1038\/s41598-024-73564-9","volume":"14","author":"NT Waz","year":"2024","unstructured":"Waz NT et al (2024) Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by Indolicidin. Sci Rep 14:23517","journal-title":"Sci Rep"},{"key":"848_CR48","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/s41541-024-01033-5","volume":"9","author":"KF Cardoso","year":"2024","unstructured":"Cardoso KF et al (2024) Intranasal influenza-vectored vaccine expressing Pneumococcal surface protein A protects against influenza and Streptococcus pneumoniae infections. NPJ Vaccines 9:246","journal-title":"NPJ Vaccines"},{"key":"848_CR49","doi-asserted-by":"publisher","first-page":"121180","DOI":"10.1016\/j.ijpharm.2021.121180","volume":"609","author":"H Xu","year":"2021","unstructured":"Xu H, Cai L, Hufnagel S, Cui Z (2021) Intranasal vaccine: factors to consider in research and development. Int J Pharm 609:121180","journal-title":"Int J Pharm"},{"key":"848_CR50","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.virusres.2004.02.028","volume":"103","author":"E de Wit","year":"2004","unstructured":"de Wit E et al (2004) Efficient generation and growth of influenza virus A\/PR\/8\/34 from eight cDNA fragments. Virus Res 103:155\u2013161","journal-title":"Virus Res"},{"key":"848_CR51","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/mi.2016.49","volume":"10","author":"A Barthelemy","year":"2017","unstructured":"Barthelemy A et al (2017) Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive Pneumococcal superinfection. Mucosal Immunol 10:460\u2013469","journal-title":"Mucosal Immunol"},{"key":"848_CR52","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/0022-1759(90)90029-U","volume":"132","author":"Y Aida","year":"1990","unstructured":"Aida Y, Pabst MJ (1990) Removal of endotoxin from protein solutions by phase separation using triton X-114. J Immunol Methods 132:191\u2013195","journal-title":"J Immunol Methods"},{"key":"848_CR53","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/cyto.b.20138","volume":"70B","author":"BL Wood","year":"2006","unstructured":"Wood BL, Levin GR (2006) Interactions between mouse IgG2 antibodies are common and mediated by plasma C1q. Cytometry B Clin Cytom 70B:321\u2013328","journal-title":"Cytometry B Clin Cytom"},{"key":"848_CR54","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/0161-5890(84)90103-2","volume":"21","author":"RJ Leatherbarrow","year":"1984","unstructured":"Leatherbarrow RJ, Dwek RA (1984) Binding of complement subcomponent Clq to mouse iggl, IgG2a AND IgG2b: A novel Clq binding assay. Mol Immunol 21:321\u2013327","journal-title":"Mol Immunol"},{"key":"848_CR55","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1365-2249.2009.04081.x","volume":"160","author":"S Aschermann","year":"2010","unstructured":"Aschermann S, Lux A, Baerenwaldt A, Biburger M, Nimmerjahn F (2010) The other side of Immunoglobulin G: suppressor of inflammation. Clin Exp Immunol 160:161\u2013167","journal-title":"Clin Exp Immunol"},{"key":"848_CR56","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1093\/infdis\/165.1.34","volume":"165","author":"K Oishi","year":"1992","unstructured":"Oishi K, Koles NL, Guelde G, Pollack M (1992) Antibacterial and protective properties of monoclonal antibodies reactive with Escherichia coli O111:B4 lipopolysaccharide: relation to antibody isotype and complement-fixing activity. J Infect Dis 165:34\u201345","journal-title":"J Infect Dis"},{"key":"848_CR57","doi-asserted-by":"publisher","first-page":"6718","DOI":"10.1128\/IAI.69.11.6718-6724.2001","volume":"69","author":"BP Arulanandam","year":"2001","unstructured":"Arulanandam BP, Lynch JM, Briles DE, Hollingshead S, Metzger DW (2001) Intranasal vaccination with Pneumococcal surface protein A and interleukin-12 augments antibody-mediated opsonization and protective immunity against Streptococcus pneumoniae infection. Infect Immun 69:6718\u20136724","journal-title":"Infect Immun"},{"key":"848_CR58","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1172\/JCI6310","volume":"104","author":"EN Janoff","year":"1999","unstructured":"Janoff EN et al (1999) Killing of Streptococcus pneumoniae by capsular polysaccharide\u2013specific polymeric iga, complement, and phagocytes. J Clin Invest 104:1139\u20131147","journal-title":"J Clin Invest"},{"key":"848_CR59","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.4049\/jimmunol.1000831","volume":"185","author":"Y Fukuyama","year":"2010","unstructured":"Fukuyama Y et al (2010) Secretory-IgA antibodies play an important role in the immunity to Streptococcus pneumoniae. J Immunol 185:1755\u20131762","journal-title":"J Immunol"},{"key":"848_CR60","doi-asserted-by":"publisher","first-page":"4576","DOI":"10.4049\/jimmunol.173.7.4576","volume":"173","author":"K Sun","year":"2004","unstructured":"Sun K, Johansen F-E, Eckmann L, Metzger DW (2004) An important role for polymeric Ig Receptor-Mediated transport of IgA in protection against Streptococcus pneumoniae nasopharyngeal Carriage1. J Immunol 173:4576\u20134581","journal-title":"J Immunol"},{"key":"848_CR61","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/mi.2013.41","volume":"7","author":"EN Janoff","year":"2014","unstructured":"Janoff EN et al (2014) Pneumococcal IgA1 protease subverts specific protection by human IgA1. Mucosal Immunol 7:249\u2013256","journal-title":"Mucosal Immunol"},{"key":"848_CR62","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/mi.2014.55","volume":"8","author":"AM Roche","year":"2015","unstructured":"Roche AM, Richard AL, Rahkola JT, Janoff EN, Weiser JN (2015) Antibody blocks acquisition of bacterial colonization through agglutination. Mucosal Immunol 8:176\u2013185","journal-title":"Mucosal Immunol"},{"key":"848_CR63","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1128\/iai.59.1.222-228.1991","volume":"59","author":"LS McDaniel","year":"1991","unstructured":"McDaniel LS, Sheffield JS, Delucchi P, Briles DE (1991) PspA, a surface protein of Streptococcus pneumoniae, is capable of eliciting protection against Pneumococci of more than one capsular type. Infect Immun 59:222\u2013228","journal-title":"Infect Immun"},{"key":"848_CR64","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1128\/CVI.00177-08","volume":"15","author":"MM M","year":"2008","unstructured":"M MM et al (2008) Distribution of Pneumococcal surface protein A families 1 and 2 among Streptococcus pneumoniae isolates from children in Finland who had acute otitis media or were nasopharyngeal carriers. Clin Vaccine Immunol 15:1555\u20131563","journal-title":"Clin Vaccine Immunol"},{"key":"848_CR65","doi-asserted-by":"publisher","first-page":"3890","DOI":"10.1016\/j.vaccine.2004.04.009","volume":"22","author":"MCC Brandileone","year":"2004","unstructured":"Brandileone MCC et al (2004) Typing of Pneumococcal surface protein A (PspA) in Streptococcus pneumoniae isolated during epidemiological surveillance in brazil: towards novel Pneumococcal protein vaccines. Vaccine 22:3890\u20133896","journal-title":"Vaccine"},{"key":"848_CR66","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1128\/CVI.00400-07","volume":"15","author":"DM Ferreira","year":"2008","unstructured":"Ferreira DM, Darrieux M, Oliveira MLS, Leite LCC, Miyaji EN (2008) Optimized immune response elicited by a DNA vaccine expressing Pneumococcal surface protein a is characterized by a balanced Immunoglobulin G1 (IgG1)\/IgG2a ratio and proinflammatory cytokine production. Clin Vaccine Immunol 15:499\u2013505","journal-title":"Clin Vaccine Immunol"},{"key":"848_CR67","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.micpath.2010.02.009","volume":"48","author":"DM Ferreira","year":"2010","unstructured":"Ferreira DM et al (2010) Protection against nasal colonization with Streptococcus pneumoniae by parenteral immunization with a DNA vaccine encoding PspA (Pneumococcal surface protein A). Microb Pathog 48:205\u2013213","journal-title":"Microb Pathog"},{"key":"848_CR68","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.micpath.2012.08.007","volume":"53","author":"CFM Vadesilho","year":"2012","unstructured":"Vadesilho CFM et al (2012) Characterization of the antibody response elicited by immunization with Pneumococcal surface protein A (PspA) as Recombinant protein or DNA vaccine and analysis of protection against an intranasal lethal challenge with Streptococcus pneumoniae. Microb Pathog 53:243\u2013249","journal-title":"Microb Pathog"},{"key":"848_CR69","first-page":"467","volume":"5","author":"KPM van Kessel","year":"2014","unstructured":"van Kessel KPM, Bestebroer J, van Strijp JAG (2014) Neutrophil-mediated phagocytosis of Staphylococcus aureus. Front Immunol 5:467","journal-title":"Front Immunol"},{"key":"848_CR70","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1111\/j.1440-1843.2010.01814.x","volume":"15","author":"GK Paterson","year":"2010","unstructured":"Paterson GK, Orihuela CJ (2010) Pneumococci: immunology of the innate host response. Respirology 15:1057\u20131063","journal-title":"Respirology"},{"key":"848_CR71","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/mi.2014.95","volume":"8","author":"R Wilson","year":"2015","unstructured":"Wilson R et al (2015) Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses. Mucosal Immunol 8:627\u2013639","journal-title":"Mucosal Immunol"},{"key":"848_CR72","doi-asserted-by":"publisher","first-page":"4430","DOI":"10.1016\/j.vaccine.2015.06.077","volume":"33","author":"L Zhang","year":"2015","unstructured":"Zhang L et al (2015) Humoral immune responses to Streptococcus pneumoniae in the setting of HIV-1 infection. Vaccine 33:4430\u20134436","journal-title":"Vaccine"},{"key":"848_CR73","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1016\/j.vaccine.2019.12.023","volume":"38","author":"S Sterrett","year":"2020","unstructured":"Sterrett S et al (2020) Peripheral CD4 T follicular cells induced by a conjugated Pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals. Vaccine 38:1778\u20131786","journal-title":"Vaccine"},{"key":"848_CR74","doi-asserted-by":"publisher","first-page":"2336358","DOI":"10.1080\/21645515.2024.2336358","volume":"20","author":"M Akkoyunlu","year":"2024","unstructured":"Akkoyunlu M (2024) State of Pneumococcal vaccine immunity. Hum Vaccin Immunother 20:2336358","journal-title":"Hum Vaccin Immunother"},{"key":"848_CR75","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1099\/jmm.0.46217-0","volume":"55","author":"DM Ferreira","year":"2006","unstructured":"Ferreira DM et al (2006) DNA vaccines expressing Pneumococcal surface protein A (PspA) elicit protection levels comparable to Recombinant protein. J Med Microbiol 55:375\u2013378","journal-title":"J Med Microbiol"},{"key":"848_CR76","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.jconrel.2024.02.028","volume":"368","author":"TC Rodrigues","year":"2024","unstructured":"Rodrigues TC et al (2024) Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against Pneumococcus. J Controll Release 368:184\u2013198","journal-title":"J Controlled Release"},{"key":"848_CR77","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.1128\/IAI.70.9.5086-5090.2002","volume":"70","author":"EN Miyaji","year":"2002","unstructured":"Miyaji EN et al (2002) Analysis of serum cross-reactivity and cross-protection elicited by immunization with DNA vaccines against Streptococcus pneumoniae expressing PspA fragments from different clades. Infect Immun 70:5086\u20135090","journal-title":"Infect Immun"},{"key":"848_CR78","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1099\/jmm.0.47661-0","volume":"57","author":"M Darrieux","year":"2008","unstructured":"Darrieux M et al (2008) Recognition of Pneumococcal isolates by antisera raised against PspA fragments from different clades. J Med Microbiol 57:273\u2013278","journal-title":"J Med Microbiol"},{"key":"848_CR79","doi-asserted-by":"publisher","first-page":"e0191692","DOI":"10.1371\/journal.pone.0191692","volume":"13","author":"TC Rodrigues","year":"2018","unstructured":"Rodrigues TC et al (2018) Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against Pneumococcal infection. PLoS ONE 13:e0191692","journal-title":"PLoS ONE"},{"key":"848_CR80","doi-asserted-by":"publisher","first-page":"958","DOI":"10.3389\/fimmu.2018.00958","volume":"9","author":"G-M Lilienthal","year":"2018","unstructured":"Lilienthal G-M et al (2018) Potential of murine IgG1 and human IgG4 to inhibit the classical complement and Fc\u03b3 receptor activation pathways. Front Immunol 9:958","journal-title":"Front Immunol"},{"key":"848_CR81","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.molimm.2015.01.028","volume":"67","author":"JPM Melis","year":"2015","unstructured":"Melis JPM et al (2015) Complement in therapy and disease: regulating the complement system with antibody-based therapeutics. Mol Immunol 67:117\u2013130","journal-title":"Mol Immunol"},{"key":"848_CR82","doi-asserted-by":"publisher","first-page":"e80034","DOI":"10.1371\/journal.pone.0080034","volume":"8","author":"B Brandenburg","year":"2013","unstructured":"Brandenburg B et al (2013) Mechanisms of hemagglutinin targeted influenza virus neutralization. PLoS ONE 8:e80034","journal-title":"PLoS ONE"},{"key":"848_CR83","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1038\/s41590-018-0231-y","volume":"19","author":"SP Jochems","year":"2018","unstructured":"Jochems SP et al (2018) Inflammation induced by influenza virus impairs human innate immune control of Pneumococcus. Nat Immunol 19:1299\u20131308","journal-title":"Nat Immunol"},{"key":"848_CR84","doi-asserted-by":"publisher","first-page":"12304","DOI":"10.1128\/JVI.01269-12","volume":"86","author":"L Wenjing","year":"2012","unstructured":"Wenjing L, Bruno M, M MT (2012) Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of \u03b3\u03b4 T cells. J Virol 86:12304\u201312312","journal-title":"J Virol"},{"key":"848_CR85","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/nm1765","volume":"14","author":"K Sun","year":"2008","unstructured":"Sun K, Metzger DW (2008) Inhibition of pulmonary antibacterial defense by interferon-\u03b3 during recovery from influenza infection. Nat Med 14:558\u2013564","journal-title":"Nat Med"},{"key":"848_CR86","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.3389\/fimmu.2017.01799","volume":"8","author":"LP Tavares","year":"2017","unstructured":"Tavares LP et al (2017) CXCR1\/2 antagonism is protective during influenza and post-influenza pneumococcal infection. Front Immunol 8:1799","journal-title":"Front Immunol"},{"key":"848_CR87","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.4049\/jimmunol.1300014","volume":"191","author":"HE Ghoneim","year":"2013","unstructured":"Ghoneim HE, Thomas PG, McCullers JA (2013) Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol 191:1250\u20131259","journal-title":"J Immunol"},{"key":"848_CR88","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.4049\/jimmunol.2000094","volume":"205","author":"AK Verma","year":"2020","unstructured":"Verma AK, Bansal S, Bauer C, Muralidharan A, Sun K (2020) Influenza infection induces alveolar macrophage dysfunction and thereby enables noninvasive Streptococcus pneumoniae to cause deadly pneumonia. J Immunol 205:1601\u20131607","journal-title":"J Immunol"}],"container-title":["Medical Microbiology and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00430-025-00848-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00430-025-00848-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00430-025-00848-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T13:01:42Z","timestamp":1767099702000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00430-025-00848-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":88,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["848"],"URL":"https:\/\/doi.org\/10.1007\/s00430-025-00848-w","relation":{},"ISSN":["0300-8584","1432-1831"],"issn-type":[{"value":"0300-8584","type":"print"},{"value":"1432-1831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,29]]},"assertion":[{"value":"4 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39"}}