{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:13:03Z","timestamp":1787728383931,"version":"build-2784847793"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>\n                    Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts older adults aged \u226565\u00a0years. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    , with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2\u20133\u00a0months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (18\u201322\u00a0months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.\n                  <\/jats:p>","DOI":"10.3389\/fragi.2021.798868","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:57:53Z","timestamp":1640138273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection"],"prefix":"10.3389","volume":"2","author":[{"given":"Manmeet","family":"Bhalla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roozbeh","family":"Nayerhoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essi Y. I.","family":"Tchalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexsandra","family":"Abamonte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongwon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaunna R.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaine A.","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa N.","family":"Bou Ghanem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/s0882-4010(95)90125-6","article-title":"Virulence of Streptococcus Pneumoniae in Mice: a Standardized Method for Preparation and Frozen Storage of the Experimental Bacterial Inoculum","volume":"18","author":"Aaberge","year":"1995","journal-title":"Microb. Pathogenesis"},{"key":"B2","doi-asserted-by":"publisher","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":"B3","doi-asserted-by":"publisher","first-page":"453","DOI":"10.2147\/CIA.S29675","article-title":"Pneumonia Immunization in Older Adults: Review of Vaccine Effectiveness and Strategies","volume":"7","author":"Assaad","year":"2012","journal-title":"Clin. Interv. Aging"},{"key":"B4","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1513\/annalsats.201511-778fr","article-title":"Pneumococcal Vaccination Strategies. An Update and Perspective","volume":"13","author":"Berical","year":"2016","journal-title":"Ann. ATS"},{"key":"B5","doi-asserted-by":"publisher","first-page":"Iai0025821","DOI":"10.1128\/iai.00258-21","article-title":"Transcriptome Profiling Reveals CD73 and Age-Driven Changes in Neutrophil Responses against Streptococcus Pneumoniae","volume":"89","author":"Bhalla","year":"2021","journal-title":"Infect. Immun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e13141","DOI":"10.1111\/cmi.13141","article-title":"A1 Adenosine Receptor Signaling Reduces Streptococcus Pneumoniae Adherence to Pulmonary Epithelial Cells by Targeting Expression of Platelet-Activating Factor Receptor","volume":"22","author":"Bhalla","year":"2020","journal-title":"Cell Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/2021.10.18.464850","article-title":"Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts against <em>S. Pneumoniae<\/em> Infection","volume":"2021","author":"Bhalla","year":"2021","journal-title":"bioRxiv."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e13218","DOI":"10.1111\/acel.13218","article-title":"Extracellular Adenosine Signaling Reverses the Age-Driven Decline in the Ability of Neutrophils to Kill Streptococcus Pneumoniae","volume":"19","author":"Bhalla","year":"2020","journal-title":"Aging Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/978-1-0716-0795-4_33","article-title":"Testing Anti-pneumococcal Antibody Function Using Bacteria and Primary Neutrophils","volume":"2183","author":"Bhalla","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"5115","DOI":"10.4049\/jimmunol.1300522","article-title":"Systemic Disease duringStreptococcus pneumoniaeAcute Lung Infection Requires 12-lipoxygenase-dependent Inflammation","volume":"191","author":"Bhowmick","year":"2013","journal-title":"J.I."},{"key":"B11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/cei.12881","article-title":"Innate Immune Responses in the Ageing Lung","volume":"187","author":"Boe","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1056\/nejmoa1408544","article-title":"Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults","volume":"372","author":"Bonten","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3739","DOI":"10.4049\/jimmunol.1701065","article-title":"Nasopharyngeal Exposure to Streptococcus Pneumoniae Induces Extended Age-dependent Protection against Pulmonary Infection Mediated by Antibodies and CD138+ Cells","volume":"200","author":"Bou Ghanem","year":"2018","journal-title":"J.I."},{"key":"B14","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s10522-011-9353-4","article-title":"B Cell Immunosenescence: Different Features of Naive and Memory B Cells in Elderly","volume":"12","author":"Buffa","year":"2011","journal-title":"Biogerontology"},{"key":"B15","unstructured":"Centers for Disease Control and Prevention2013"},{"key":"B16","unstructured":"Centers for Disease Control and Prevention2021"},{"key":"B17","article-title":"Emerging Infections Program Network, Streptococcus Pneumoniae","year":"2017"},{"key":"B18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3389\/fcimb.2014.00194","article-title":"Streptococcus Pneumoniae Biofilm Formation and Dispersion during Colonization and Disease","volume":"4","author":"Chao","year":"2014","journal-title":"Front Cell Infect Microbiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.it.2009.05.002","article-title":"Vaccination in the Elderly: an Immunological Perspective","volume":"30","author":"Chen","year":"2009","journal-title":"Trends Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/1471-2180-8-216","article-title":"Acinetobacter Baumannii Invades Epithelial Cells and Outer Membrane Protein A Mediates Interactions with Epithelial Cells","volume":"8","author":"Choi","year":"2008","journal-title":"BMC Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1097\/smj.0b013e318181d5b5","article-title":"Pneumonia in the Elderly: a Review of the Epidemiology, Pathogenesis, Microbiology, and Clinical Features","volume":"101","author":"Chong","year":"2008","journal-title":"South. Med. J."},{"key":"B22","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/377435a0","article-title":"Streptococcus Pneumoniae Anchor to Activated Human Cells by the Receptor for Platelet-Activating Factor","volume":"377","author":"Cundell","year":"1995","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"33507","DOI":"10.1073\/pnas.2010428117","article-title":"An In Vivo Atlas of Host-Pathogen Transcriptomes during Streptococcus Pneumoniae Colonization and Disease","volume":"117","author":"D'Mello","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B24","doi-asserted-by":"publisher","first-page":"27","DOI":"10.5863\/1551-6776-21.1.27","article-title":"A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens","volume":"21","author":"Daniels","year":"2016","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1097\/00006454-199906000-00015","article-title":"Pneumococcal Conjugate Vaccines","volume":"18","author":"Eskola","year":"1999","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.arr.2010.08.004","article-title":"Age Effects on B Cells and Humoral Immunity in Humans","volume":"10","author":"Frasca","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e00937","DOI":"10.1128\/mBio.00937-20","article-title":"A New Pneumococcal Capsule Type, 10D, Is the 100th Serotype and Has a Large Cps Fragment from an Oral Streptococcus","volume":"11","author":"Ganaie","year":"2020","journal-title":"mBio"},{"key":"B28","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s10522-015-9614-8","article-title":"Immune Ageing and Susceptibility to Streptococcus Pneumoniae","volume":"17","author":"Gon\u00e7alves","year":"2016","journal-title":"Biogerontology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1042\/cs20171157","article-title":"T Follicular Helper Cell Development and Functionality in Immune Ageing","volume":"132","author":"Gustafson","year":"2018","journal-title":"Clin. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.2217\/17460913.3.1.23","article-title":"Serotype-specific Problems Associated with Pneumococcal Conjugate Vaccination","volume":"3","author":"Hanage","year":"2008","journal-title":"Future Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.idc.2017.07.015","article-title":"Bacterial Pneumonia in Older Adults","volume":"31","author":"Henig","year":"2017","journal-title":"Infect. Dis. Clin. North America"},{"key":"B32","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1021\/acsinfecdis.8b00100","article-title":"Engineering a Next-Generation Glycoconjugate-like Streptococcus Pneumoniae Vaccine","volume":"4","author":"Hill","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1016\/j.vaccine.2011.02.088","article-title":"Healthcare Utilization and Cost of Pneumococcal Disease in the United States","volume":"29","author":"Huang","year":"2011","journal-title":"Vaccine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3594","DOI":"10.1016\/j.vaccine.2013.04.084","article-title":"Influence of Initial Vaccination with 13-valent Pneumococcal Conjugate Vaccine or 23-valent Pneumococcal Polysaccharide Vaccine on Anti-pneumococcal Responses Following Subsequent Pneumococcal Vaccination in Adults 50 Years and Older","volume":"31","author":"Jackson","year":"2013","journal-title":"Vaccine"},{"key":"B35","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/s1473-3099(04)00931-4","article-title":"Pneumonia in the Very Old","volume":"4","author":"Janssens","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e1701797","DOI":"10.1126\/sciadv.1701797","article-title":"Comprehensive Vaccine Design for Commensal Disease Progression","volume":"3","author":"Jones","year":"2017","journal-title":"Sci. Adv."},{"key":"B37","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1093\/bfgp\/4.3.241","article-title":"Susceptibility and Resistance to Pneumococcal Disease in Mice","volume":"4","author":"Kadioglu","year":"2005","journal-title":"Brief. Funct. Genomics Proteomics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nrmicro1871","article-title":"The Role of Streptococcus Pneumoniae Virulence Factors in Host Respiratory Colonization and Disease","volume":"6","author":"Kadioglu","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e01792","DOI":"10.1128\/mBio.01792-15","article-title":"Nonencapsulated Streptococcus Pneumoniae: Emergence and Pathogenesis","volume":"7","author":"Keller","year":"2016","journal-title":"mBio"},{"key":"B40","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/s2213-2600(13)70165-6","article-title":"Immunosenescence and Pneumococcal Disease: an Imbalance in Host-Pathogen Interactions","volume":"2","author":"Krone","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jim.2018.08.002","article-title":"Measuring Immune Responses to Pneumococcal Vaccines","volume":"461","author":"LaFon","year":"2018","journal-title":"J. Immunological Methods"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1017\/s0950268810002402","article-title":"Outcomes of Hospitalized Patients with Bacteraemic and Non-bacteraemic Community-Acquired Pneumonia Caused by Streptococcus Pneumoniae","volume":"139","author":"Lin","year":"2011","journal-title":"Epidemiol. Infect."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1016\/S1473-3099(18)30310-4","article-title":"Estimates of the Global, Regional, and National Morbidity, Mortality, and Aetiologies of Lower Respiratory Infections in 195 Countries, 1990-2016: a Systematic Analysis for the Global Burden of Disease Study 2016","volume":"18","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e00438","DOI":"10.1128\/mBio.00438-13","article-title":"Interkingdom Signaling Induces Streptococcus Pneumoniae Biofilm Dispersion and Transition from Asymptomatic Colonization to Disease","volume":"4","author":"Marks","year":"2013","journal-title":"mBio"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2744","DOI":"10.1128\/iai.00488-12","article-title":"Pneumococcal Interactions with Epithelial Cells Are Crucial for Optimal Biofilm Formation and ColonizationIn VitroandIn Vivo","volume":"80","author":"Marks","year":"2012","journal-title":"Infect. Immun."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.15585\/mmwr.mm6846a5","article-title":"Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged \u226565 Years: Updated Recommendations of the Advisory Committee on Immunization Practices","volume":"68","author":"Matanock","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.3390\/ma12172809","article-title":"Design Variation of a Dual-Antigen Liposomal Vaccine Carrier System","volume":"12","author":"Nayerhoda","year":"2019","journal-title":"Materials (Basel)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/978-1-0716-0795-4_26","article-title":"Liposomal Dual Delivery of Both Polysaccharide and Protein Antigens","volume":"2183","author":"Nayerhoda","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1099\/0022-1317-51-2-98","article-title":"The Pneumococcus: Carriage, Disease and Conjugate Vaccines","volume":"51","author":"Obaro","year":"2002","journal-title":"J. Med. Microbiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"583019","DOI":"10.3389\/fimmu.2020.583019","article-title":"Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly","volume":"11","author":"Pereira","year":"2020","journal-title":"Front. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1002\/eji.201546178","article-title":"Aging of the Immune System: Focus on Inflammation and Vaccination","volume":"46","author":"Pinti","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1136\/adc.2010.191718","article-title":"Invasive Pneumococcal Disease","volume":"96","author":"Randle","year":"2011","journal-title":"Arch. Dis. Child. - Edu. Pract."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1016\/j.vaccine.2008.11.098","article-title":"Immunological Responses to Pneumococcal Vaccine in Frail Older People","volume":"27","author":"Ridda","year":"2009","journal-title":"Vaccine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1016\/j.vaccine.2010.12.121","article-title":"Aging Reduces the Functionality of Anti-pneumococcal Antibodies and the Killing of Streptococcus Pneumoniae by Neutrophil Phagocytosis","volume":"29","author":"Simell","year":"2011","journal-title":"Vaccine"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00653-20","article-title":"Older but Not Wiser: the Age-Driven Changes in Neutrophil Responses during Pulmonary Infections","volume":"89","author":"Simmons","year":"2021","journal-title":"Infect. Immun."},{"key":"B56","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1002\/JLB.4MA0120-115RR","article-title":"Extracellular Adenosine Enhances the Ability of PMNs to Kill Streptococcus Pneumoniae by Inhibiting IL-10 Production","volume":"108","author":"Siwapornchai","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/s10156-013-0601-1","article-title":"Pneumococcal Vaccine and Opsonic Pneumococcal Antibody","volume":"19","author":"Song","year":"2013","journal-title":"J. Infect. Chemother."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.4049\/jimmunol.0900688","article-title":"Human Neutrophils KillStreptococcus Pneumoniaevia Serine Proteases","volume":"183","author":"Standish","year":"2009","journal-title":"J. Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/s1473-3099(17)30049-x","article-title":"Serotype-specific Effectiveness of 23-valent Pneumococcal Polysaccharide Vaccine against Pneumococcal Pneumonia in Adults Aged 65 Years or Older: a Multicentre, Prospective, Test-Negative Design Study","volume":"17","author":"Suzuki","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e50586","DOI":"10.3791\/50586","article-title":"Isolation, Purification and Labeling of Mouse Bone Marrow Neutrophils for Functional Studies and Adoptive Transfer Experiments","volume":"77","author":"Swamydas","year":"2013","journal-title":"J. Vis. Exp."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/infdis\/jiaa242","article-title":"Neutrophils Are Required during Immunization with the Pneumococcal Conjugate Vaccine for Protective Antibody Responses and Host Defense against Infection","volume":"222","author":"Tchalla","year":"2020","journal-title":"J. Infect. Dis."},{"key":"B62","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1126\/science.1061217","article-title":"Complete Genome Sequence of a Virulent Isolate of Streptococcus Pneumoniae","volume":"293","author":"Tettelin","year":"2001","journal-title":"Science"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/s0140-6736(09)61114-4","article-title":"Pathogenesis, Treatment, and Prevention of Pneumococcal Pneumonia","volume":"374","author":"van der Poll","year":"2009","journal-title":"The Lancet"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1093\/cid\/civ686","article-title":"The Impact of Age on the Efficacy of 13-valent Pneumococcal Conjugate Vaccine in Elderly","volume":"61","author":"van Werkhoven","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev-immunol-041015-055605","article-title":"Follicular Helper T Cells","volume":"34","author":"Vinuesa","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1086\/529197","article-title":"Biology of Immune Responses to Vaccines in Elderly Persons","volume":"46","author":"Weinberger","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"B67","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41579-018-0001-8","article-title":"Streptococcus Pneumoniae: Transmission, Colonization and Invasion","volume":"16","author":"Weiser","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s12913-016-1432-4","article-title":"Rates and Costs of Invasive Pneumococcal Disease and Pneumonia in Persons with Underlying Medical Conditions","volume":"16","author":"Weycker","year":"2016","journal-title":"BMC Health Serv. Res."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1093\/infdis\/jis240","article-title":"Aging Population and Future burden of Pneumococcal Pneumonia in the United States","volume":"205","author":"Wroe","year":"2012","journal-title":"J. Infect. Dis."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.4049\/jimmunol.1700539","article-title":"Neutrophil-Derived Cytosolic PLA2\u03b1 Contributes to Bacterial-Induced Neutrophil Transepithelial Migration","volume":"199","author":"Yonker","year":"2017","journal-title":"J.I."}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2021.798868\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:57:58Z","timestamp":1640138278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2021.798868\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":70,"alternative-id":["10.3389\/fragi.2021.798868"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2021.798868","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.10.18.464850","asserted-by":"object"}]},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]},"article-number":"798868"}}