{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:11:37Z","timestamp":1793142697113,"version":"4.5.0"},"reference-count":135,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82172267"],"award-info":[{"award-number":["82172267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92169206"],"award-info":[{"award-number":["92169206"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92269113"],"award-info":[{"award-number":["92269113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Youth Research Fund of Zhongshan Hospital, Fudan University","award":["2022ZSQN16"],"award-info":[{"award-number":["2022ZSQN16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Streptococcus pneumoniae (S. pneumoniae) is a leading cause of pneumonia, meningitis, and sepsis worldwide, posing a major threat to young children and older adults. In China, it is a key pathogen responsible for life-threatening invasive pneumococcal disease (IPD)\u2014including pneumonia, bacteremia, and meningitis\u2014and contributes substantially to hospitalizations and deaths each year. The high disease burden, together with rising antibiotic resistance, underscores the urgent need for more effective strategies for prevention and control. Currently, the most established pneumococcal vaccines include polysaccharide vaccines (e.g., PPV23) and polysaccharide conjugate vaccines (e.g., PCV13), both of which provide effective protection against pneumococcal infections. However, challenges remain, such as the T-cell-independent nature of polysaccharide antigens and inadequate coverage against prevalent strains, which hinder to improve their overall effectiveness. In this review, we trace the progression from pneumococcal pathogenesis to vaccine development. We first outline the mechanisms of colonization, invasion, and key virulence factors, and then critically summarize historical and current vaccine strategies. A systematic literature search was conducted in PubMed and Web of Science (2010\u2013present) using relevant keyword and MeSH combinations. A total of 10,273 articles were identified from PubMed; after removal of duplicates and non-full-text records, 260 research articles were included in the final analysis. Based on this body of evidence, we evaluate emerging approaches toward broadly protective, serotype-independent vaccines and discuss how advances in antigen design, delivery systems, and adjuvants may further optimize next-generation pneumococcal vaccines.<\/jats:p>","DOI":"10.3390\/vaccines14030208","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Future Pneumococcal Vaccines: Shifting from Capsular Polysaccharides to Protein-Based Immunogens"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4970-8031","authenticated-orcid":false,"given":"Ruodan","family":"Zheng","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China"},{"name":"Clinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Shu","sequence":"additional","affiliation":[{"name":"Clinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Xie","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China"},{"name":"Clinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-7707","authenticated-orcid":false,"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China"},{"name":"Clinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China"},{"name":"Clinical Center of Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127221","DOI":"10.1016\/j.micres.2022.127221","article-title":"Epidemiological Characteristics and Antibiotic Resistance Mechanisms of Streptococcus Pneumoniae: An Updated Review","volume":"266","author":"Li","year":"2023","journal-title":"Microbiol. 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