References
-
Collaborators, G. B. D. A. R Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 400, 2221–2248 (2022).
-
Shi, T. et al. Global and regional burden of hospital admissions for pneumonia in older adults: a systematic review and meta-analysis. J. Infect. Dis. 222, S570–S576 (2020).
-
LeBlanc, J. J. et al. Burden of vaccine-preventable pneumococcal disease in hospitalized adults: a Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) network study. Vaccine 35, 3647–3654 (2017).
-
Yu, J. et al. New pneumococcal serotype 20C is a WciG O-acetyltransferase deficient variant of canonical serotype 20B. Microbiol. Spectr. 13, e0244324 (2025).
-
Ganaie, F. et al. A new pneumococcal capsule type, 10D, is the 100th serotype and has a large cps fragment from an oral Streptococcus. mBio 11, https://doi.org/10.1128/mBio.00937-20 (2020).
-
Ganaie, F. A. et al. Discovery and characterization of pneumococcal serogroup 36 capsule subtypes, serotypes 36A and 36B. J. Clin. Microbiol. 61, e0002423 (2023).
-
Collaborators, G. B. D. L. R. I 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. Lancet Infect. Dis. 18, 1191–1210 (2018).
-
Kalizang’oma, A. et al. Clonal expansion of a Streptococcus pneumoniae serotype 3 capsule variant sequence type 700 with enhanced vaccine escape potential after 13-valent pneumococcal conjugate vaccine introduction. J. Infect. Dis. 230, e189–e198 (2024).
-
Candeias, C. et al. Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in National Immunization Program: a cross-sectional study. Vaccine 42, 126219 (2024).
-
von Mollendorf, C. & Ong-Lim, A. L. T. How have pneumococcal conjugate vaccines changed the pneumococcal disease landscape?. Lancet Infect. Dis. 25, 367–369 (2025).
-
Ranjbar, R. & Alam, M. Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Evid. Based Nurs. https://doi.org/10.1136/ebnurs-2022-103540 (2023).
-
Hyams, C. et al. Serotype distribution and disease severity in adults hospitalized with Streptococcus pneumoniae infection, Bristol and Bath, UK, 2006‒2022. Emerg. Infect. Dis. 29, 1953–1964 (2023).
-
Li, L. et al. Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: an updated review. Microbiol. Res. 266, 127221 (2023).
-
Kobayashi, M. et al. Use of 21-valent pneumococcal conjugate vaccine among U.S. adults: recommendations of the Advisory Committee on Immunization Practices—United States, 2024. MMWR Morb. Mortal Wkly Rep. 73, 793–798 (2024).
-
Rappuoli, R. Glycoconjugate vaccines: principles and mechanisms. Sci. Transl. Med. 10, https://doi.org/10.1126/scitranslmed.aat4615 (2018).
-
Chen, C. et al. Effect and cost-effectiveness of pneumococcal conjugate vaccination: a global modelling analysis. Lancet Glob. Health 7, e58–e67 (2019).
-
Belshe, R. B. et al. Safety, efficacy, and effectiveness of live, attenuated, cold-adapted influenza vaccine in an indicated population aged 5–49 years. Clin. Infect. Dis. 39, 920–927 (2004).
-
Eiden, J. et al. Intranasal M2SR (M2-deficient single replication) H3N2 influenza vaccine provides enhanced mucosal and serum antibodies in adults. J. Infect. Dis. 227, 103–112 (2022).
-
Babu, T. M., Jackson, L. A. & El Sahly, H. M. Next-generation SARS-CoV-2 vaccine formulations and alternative routes of administration. J. Infect. Dis. 231, 44–48 (2025).
-
Chu, K. et al. A randomized phase I trial of intranasal SARS-CoV-2 vaccine dNS1-RBD in children aged 3–17 years. NPJ Vaccines 10, 50 (2025).
-
Li, J. X. et al. Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial. Lancet Respir. Med. 10, 739–748 (2022).
-
Hirayama, S. & Nakao, R. Glycine induction method: effective production of immunoactive bacterial membrane vesicles with low endotoxin content. Methods Mol. Biol. 2414, 207–226 (2022).
-
Hirayama, S. & Nakao, R. Glycine significantly enhances bacterial membrane vesicle production: a powerful approach for isolation of LPS-reduced membrane vesicles of probiotic Escherichia coli. Microb. Biotechnol. 13, 1162–1178 (2020).
-
Nakao, R. et al. A highly immunogenic vaccine platform against encapsulated pathogens using chimeric probiotic Escherichia coli membrane vesicles. NPJ Vaccines 7, 153 (2022).
-
Musher, D. M. et al. Safety and antibody response, including antibody persistence for 5 years, after primary vaccination or revaccination with pneumococcal polysaccharide vaccine in middle-aged and older adults. J. Infect. Dis. 201, 516–524 (2010).
-
van Werkhoven, C. H., Huijts, S. M., Bolkenbaas, M., Grobbee, D. E. & Bonten, M. J. The impact of age on the efficacy of 13-valent pneumococcal conjugate vaccine in elderly. Clin. Infect. Dis. 61, 1835–1838 (2015).
-
Thevaranjan, N. et al. Streptococcus pneumoniae colonization disrupts the microbial community within the upper respiratory tract of aging mice. Infect. Immun. 84, 906–916 (2016).
-
Cubas, R. et al. Virus-like particle (VLP) lymphatic trafficking and immune response generation after immunization by different routes. J. Immunother. 32, 118–128 (2009).
-
Reddy, S. T. et al. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat. Biotechnol. 25, 1159–1164 (2007).
-
Wilson, J. T. A sweeter approach to vaccine design. Science 363, 584–585 (2019).
-
Munoz-Wolf, N. et al. Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles. Cell Rep. Med. 4, 100899 (2023).
-
Degn, S. E. & Tolar, P. Towards a unifying model for B-cell receptor triggering. Nat. Rev. Immunol. 25, 77–91 (2025).
-
Tolar, P. & Pierce, S. K. Unveiling the B cell receptor structure. Science 377, 819–820 (2022).
-
Olivo-Martinez, Y. et al. Modulation of serotonin-related genes by extracellular vesicles of the probiotic Escherichia coli Nissle 1917 in the interleukin-1beta-induced inflammation model of intestinal epithelial cells. Int. J. Mol. Sci. 25, https://doi.org/10.3390/ijms25105338 (2024).
-
Canas, M. A., Fabrega, M. J., Gimenez, R., Badia, J. & Baldoma, L. Outer membrane vesicles from probiotic and commensal Escherichia coli activate NOD1-mediated immune responses in intestinal epithelial cells. Front. Microbiol. 9, 498 (2018).
-
Jerving, S. The long road ahead for COVID-19 vaccination in Africa. Lancet 398, 827–828 (2021).
-
Loyo, E. S. L., Gonzalez, M. J. & Esparza, J. Venezuela is collapsing without COVID-19 vaccines. Lancet 397, 1806 (2021).
-
Li, X. et al. Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study. Lancet 397, 398–408 (2021).
-
Zhang, J. R. et al. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102, 827–837 (2000).
-
Briles, D. E. et al. PspA and PspC: their potential for use as pneumococcal vaccines. Microb. Drug Resist. 3, 401–408 (1997).
-
Hammerschmidt, S., Talay, S. R., Brandtzaeg, P. & Chhatwal, G. S. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol. Microbiol. 25, 1113–1124 (1997).
-
Lu, L., Lamm, M. E., Li, H., Corthesy, B. & Zhang, J. R. The human polymeric immunoglobulin receptor binds to Streptococcus pneumoniae via domains 3 and 4. J. Biol. Chem. 278, 48178–48187 (2003).
-
Iovino, F. et al. Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA. J. Clin. Investig. 126, 2821–2826 (2016).
-
Iovino, F. et al. pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion. J. Exp. Med. 214, 1619–1630 (2017).
-
Renegar, K. B., Small, P. A. Jr, Boykins, L. G. & Wright, P. F. Role of IgA versus IgG in the control of influenza viral infection in the murine respiratory tract. J. Immunol. 173, 1978–1986 (2004).
-
Renegar, K. B., Jackson, G. D. & Mestecky, J. In vitro comparison of the biologic activities of monoclonal monomeric IgA, polymeric IgA, and secretory IgA. J. Immunol. 160, 1219–1223 (1998).
-
Suzuki, T. et al. Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus. Proc. Natl. Acad. Sci. USA 112, 7809–7814 (2015).
-
Saito, S. et al. IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody. PLoS Pathog. 15, e1007427 (2019).
-
Keller, L. E., Robinson, D. A. & McDaniel, L. S. Nonencapsulated Streptococcus pneumoniae: emergence and pathogenesis. mBio 7, e01792 (2016).
-
Nissle, A. Über die Grundlagen einer neuen ursächlichen Bekämpfung der pathologischen Darmflora. Dtsch. Med. Wochenschr. 42, 1181–1184 (1916).
-
Wang, R. F. & Kushner, S. R. Construction of versatile low-copy-number vectors for cloning, sequencing and gene expression in Escherichia coli. Gene 100, 195–199 (1991).
-
Price, N. L. et al. Glycoengineered outer membrane vesicles: a novel platform for bacterial vaccines. Sci. Rep. 6, 24931 (2016).
-
Imohl, M., Reinert, R. R., Ocklenburg, C. & van der Linden, M. Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease. J. Clin. Microbiol. 48, 1291–1296 (2010).
-
Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal. Biochem. 72, 248–254 (1976).
-
Percie du Sert, N. et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 18, e3000410 (2020).
-
Asahi, Y. et al. Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines. J. Immunol. 168, 2930–2938 (2002).
-
Abdus Salam, M. et al. Establishment of an animal model using recombinant NOD.B10.D2 mice to study initial adhesion of oral streptococci. Clin. Diagn. Lab. Immunol. 11, 379–386 (2004).
-
Kawai, S., Takagi, Y., Kaneko, S. & Kurosawa, T. Effect of three types of mixed anesthetic agents alternate to ketamine in mice. Exp. Anim. 60, 481–487 (2011).
-
Bai, D., Nakao, R., Ito, A., Uematsu, H. & Senpuku, H. Immunoreactive antigens recognized in serum samples from mice intranasally immunized with Porphyromonas gingivalis outer membrane vesicles. Pathog. Dis. 73, https://doi.org/10.1093/femspd/ftu006 (2015).
-
Henckaerts, I., Durant, N., De Grave, D., Schuerman, L. & Poolman, J. Validation of a routine opsonophagocytosis assay to predict invasive pneumococcal disease efficacy of conjugate vaccine in children. Vaccine 25, 2518–2527 (2007).
-
Romero-Steiner, S. et al. Use of opsonophagocytosis for serological evaluation of pneumococcal vaccines. Clin. Vaccine Immunol. 13, 165–169 (2006).
-
Kim, K. H., Yu, J. & Nahm, M. H. Efficiency of a pneumococcal opsonophagocytic killing assay improved by multiplexing and by coloring colonies. Clin. Diagn. Lab. Immunol. 10, 616–621 (2003).
-
Burton, R. L. & Nahm, M. H. Development and validation of a fourfold multiplexed opsonization assay (MOPA4) for pneumococcal antibodies. Clin. Vaccine Immunol. 13, 1004–1009 (2006).
-
Nahm, M. H. & Burton, R. L. Protocol for multiplexed opsonophagocytic killing assay (UAB-MOPA) for antibodies against Streptococcus pneumoniae Protoc. UAB-MOPA 1–43 Version E.02, https://www.vaccine.uab.edu/index.html (2014).
