Related Topics
Articles published on Pneumococcal conjugate vaccine
Authors
Select Authors
Journals
Select Journals
Duration
Select Duration
5996 Search results
Sort by Recency
- New
- Research Article
- 10.1016/j.vaccine.2025.127991
- Jan 1, 2026
- Vaccine
- Catherine R Mcgowan + 15 more
Safety and coverage of Pneumosil pneumococcal polysaccharide conjugate vaccine (10-valent PCV) in a camp for internally displaced persons in Somaliland.
- New
- Research Article
- 10.1016/j.vaccine.2025.127996
- Jan 1, 2026
- Vaccine
- Valda Anne Struwig + 4 more
Evaluating the implementation of the 20-valent pneumococcal conjugate vaccine for paediatric immunization in Australia.
- New
- Research Article
- 10.1016/j.jiph.2025.103030
- Jan 1, 2026
- Journal of infection and public health
- María Noemí Carnalla-Barajas + 24 more
Pneumococcal meningitis in Mexico. Serotype distribution and antimicrobial resistance before and after the introduction of pneumococcal conjugate vaccines in pediatric patients. Results from the GIVEBPVac group.
- New
- Research Article
- 10.1016/j.vaccine.2025.128066
- Jan 1, 2026
- Vaccine
- Chia-Yuan Chang + 4 more
Effect of pneumococcal conjugate vaccine booster dose on prevention of invasive pneumococcal disease in British Columbia, 2003-2018.
- New
- Research Article
- 10.1016/j.vaccine.2025.128023
- Jan 1, 2026
- Vaccine
- Merve Mert Vahabi + 5 more
A single center's 25-year experience with hepatitis B and pneumoccocal vaccines in heart transplant patients: the impact of the COVID-19 pandemic.
- New
- Research Article
- 10.1016/j.vaccine.2025.127940
- Jan 1, 2026
- Vaccine
- Charles Stoecker + 5 more
Cost-effectiveness of age-based and risk-based use of the new 21-valent pneumococcal conjugate vaccine among U.S. adults.
- New
- Research Article
- 10.1016/j.micpath.2025.108210
- Jan 1, 2026
- Microbial pathogenesis
- Sandip Patil + 11 more
Pneumococcal serotypes and resistance profiles among children with and without PCV13 vaccination in Shenzhen, China.
- New
- Research Article
- 10.18203/2394-6040.ijcmph20254444
- Dec 31, 2025
- International Journal Of Community Medicine And Public Health
- Mohit Kumar + 5 more
Background: Pneumococcal infection is a major public health concern and a leading cause of death among children under five, particularly in developing countries. Pneumonia accounted for 14% of all deaths among children under five in India, with an estimated 740,180 fatalities in 2019. Although pneumonia is vaccine-preventable, low awareness and knowledge hinder access to immunisation. This study aimed to assess the knowledge and attitude of parents toward pneumococcal disease and the pneumococcal conjugate vaccine (PCV) among children under five attending the immunisation clinic of Government Medical College, Nagpur. Methods: A cross-sectional study was conducted from November 2022 to January 2023 among 340 parents/guardians of children under five who visited the immunisation clinic using a convenience sampling technique. Data were collected using a pre-tested, semi-structured questionnaire via face-to-face interviews, covering demographic details, awareness of pneumococcal disease and knowledge and attitudes regarding PCV. Data were summarised using frequencies and percentages. Results: Among the participants, 37.7% were aged 26–30 years and 33.8% had attained a graduate degree or higher. Awareness of pneumococcal disease was reported by 85.6% of parents/guardians; however, knowledge of the pneumococcal vaccine and its benefits was limited. The main reason for non-vaccination among children was unavailability of the vaccine at health facilities. Conclusions: While general awareness of pneumococcal disease was relatively high among parents, understanding of the PCV and its importance was inadequate. Strengthening parental education and ensuring consistent vaccine availability at health facilities are essential to improve PCV coverage and reduce childhood morbidity and mortality from pneumonia.
- New
- Research Article
- 10.1080/14760584.2025.2515596
- Dec 31, 2025
- Expert Review of Vaccines
- Charalampos Tzanetakos + 6 more
ABSTRACT Objective The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) and 15-valent pneumococcal conjugate vaccine (PCV15) for prevention of pneumococcal disease in the pediatric population in Greece. Methods A published decision-analytic Markov model was adapted from payer perspective, to compare PCV20 (under a 3 + 1 dosing schedule per EMA approval) with PCV13 and PCV15 (both under a 2 + 1 dosing schedule) over a 10-year time horizon. Inputs for epidemiology, serotype coverage, vaccine effectiveness, utilities, and direct medical costs (€2024) were sourced from published literature and official data. Model outcomes included number of invasive pneumococcal disease (IPD), noninvasive hospitalized pneumonia, non-hospitalized pneumonia and otitis media (OM) cases, attributable deaths, costs, quality-adjusted life-years (QALYs) for each vaccination strategy and the incremental cost-effectiveness ratios for each comparison. Scenario analyses assessed PCV20 in a 2 + 1 schedule per recent national recommendations. Results The analysis indicated that, vaccination with PCV20 compared to PCV13 and PCV15 prevents an additional 1,953 and 1,514 cases of IPD 54,956 and 42,069 noninvasive hospitalized and non-hospitalized pneumonia cases, 343,353 and 271,864 OM cases and 1,377 and 987 deaths respectively, resulting in incremental gain of 23,065 (vs PCV13) and 17,118 (vs PCV15) QALYs respectively. The lower number of pneumococcal disease cases with PCV20 compared to PCV13 and PCV15, translated to a reduction in total medical care cost of €249 M vs PCV13 and €192 M vs PCV15 over the modeled time horizon. Scenario analyses showed that PCV20 remained dominant under a 2 + 1 dosing schedule. Conclusion Vaccination with PCV20, whether in a 2 + 1 or a 3 + 1 schedule, was estimated to be a dominant vaccination strategy over PCV15 or PCV13 for the prevention of pneumococcal disease in Greek infants, as expansion of serotype coverage prevents additional morbidity and costs.
- New
- Research Article
- 10.1128/aac.01530-25
- Dec 31, 2025
- Antimicrobial agents and chemotherapy
- Joaquín Llorente + 8 more
Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. The rise of non-vaccine serotypes is a frequent phenomenon after the use of these PCVs. This study is a national surveillance that includes all pneumococcal isolates causing invasive pneumococcal disease (IPD) (4,455 isolates) in the pediatric population to analyze the changes of strains with reduced susceptibility (IPD-RS) to different antibiotics (1,458 to penicillin/1,304 to erythromycin) and the impact of PCVs and COVID-19 pandemic on antibiotic resistance. Six periods are differentiated according to this decline: pre-PCV13, early PCV13, middle PCV13, late PCV13, COVID-19, and reopening. Between 2009 and 2023, overall IPD cases in Spain decreased by over 60% in children aged 1-4 years and by approximately 50% in infants under 1 year of age. Nevertheless, an increase in IPD-RS caused by non-PCV13 serotypes was observed, with serotype 24F being the most prevalent, which is not included in the currently licensed PCVs. The introduction of PCV13 showed a substantial impact on reducing IPD in children. The COVID-19 pandemic led to a temporary decline in the burden of disease caused by resistant strains in 2020 due to non-pharmacological measures followed by a subsequent recovery.
- New
- Research Article
- 10.1080/14760584.2025.2569037
- Dec 31, 2025
- Expert Review of Vaccines
- Shahrul Mt-Isa + 4 more
ABSTRACT Background Clinical trials have compared new pneumococcal conjugative vaccines (PCVs; PCV15 and PCV20) to an established PCV (PCV13) in a routine 2 + 1 schedule. This study performed an indirect comparison of PCV15 vs. PCV20 immune responses in healthy infants and toddlers. Research design and methods Pooled, matching-adjusted PCV15 trials were indirectly compared to the analogous PCV20 trial for IgG response rate difference (RRD) and geometric mean concentration ratio (GMR) at the post-primary series (PPS) and post-toddler dose (PTD) timepoints. Results At PPS, PCV15 was non-inferior for RRD and GMR as compared to PCV20 for all PCV13 serotypes. Moreover, PCV15 was superior to PCV20 for the RRDs of serotypes 1, 3, 4, 5, 6B, 9V, and 23F and GMRs of serotypes 3, 4, 5, 6B, 9V, and 23F at PPS. At PTD, RRDs were comparable for all PCV13 serotypes, except serotype 3, for which PCV15 was superior. PCV15 was superior for the GMRs of serotypes 3, 6B, and 23F, and comparable for the remaining serotypes at PTD. RRDs for serotypes 22F and 33F were non-inferior at both PPS and PTD. Conclusion In a 2 + 1 schedule, PCV15 demonstrates immunogenicity comparable or superior to PCV20 across PCV13 serotypes, especially for serotype 3.
- New
- Research Article
- 10.1080/21645515.2025.2583614
- Dec 31, 2025
- Human Vaccines & Immunotherapeutics
- Qiuyan Yu + 8 more
ABSTRACT There is limited information on the association between burden of pneumococcal disease and vaccination. This study aimed to assess pneumococcal disease burden among adults in Hong Kong by estimating incidence rate (IR), case fatality rate (CFR), healthcare resource utilization and costs before and after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into Hong Kong’s childhood immunization program (CIP) in 2011. Adults ≥18 years hospitalized with invasive pneumococcal disease (IPD) and pneumonia from 2005 to 2019 were identified from the Clinical Data Analysis and Reporting System (CDARS). Interrupted time series analysis (ITSA) was performed and incidence rate ratio (IRR) was computed to compare baseline and trend of IRs between pre-introduction (2005–2010) and post-introduction (2012–2019) of PCV13. Overall IPD and pneumonia IRs were 0.78 and 5.34 episodes per 100,000 person-years, respectively. ITSA showed no changes in baseline IPD IR (IRR = 0.82; P value = .447) and trend of IR (IRR = 0.98; P value = .112). There was no difference in baseline pneumonia IR (IRR = 0.81; P value = .075), but a marginal (small but statistically significant) reduction in trend was observed in the post-PCV13 period (IRR = 0.98; P value = .019). CFR was 24.12% for IPD and higher at 30.06% for pneumonia. The average total costs per pneumonia episode were higher in the post-PCV13 period (2,975 vs. 2,810 Hong Kong Dollar). IPD and pneumonia incidence fluctuated over the study period. After PCV13 introduction into Hong Kong’s CIP, there was only a marginal reduction in trend of pneumonia among adults. CFRs of IPD and pneumonia were high, and disease burden remained substantial.
- New
- Research Article
- 10.1128/jcm.00984-25
- Dec 30, 2025
- Journal of clinical microbiology
- Hyun Jung Ji + 9 more
Streptococcus pneumoniae (pneumococcus) is a leading cause of community-acquired pneumonia and invasive diseases, particularly among children and the elderly. The introduction of pneumococcal conjugate vaccines has significantly reduced invasive pneumococcal disease, but the prevalence of non-vaccine serotypes and newly emerging serotypes is increasing globally. Thus, accurate serotyping is essential for epidemiological surveillance and the development of next-generation multivalent pneumococcal vaccines. Conventional serotyping methods, including multiplex polymerase chain reaction (mPCR), monoclonal antibody (mAb) assays, and Quellung reaction using rabbit antisera, are limited by serotype coverage and cross-reactivity, making the detection of new or emerging serotypes challenging. In this study, we developed a nanopore Cas9-targeted serotyping (nCATSerotyping) platform, which employs Cas9-mediated enrichment of the capsular polysaccharide synthesis locus followed by Oxford Nanopore sequencing. Applying this method to 276 clinical pneumococcal isolates collected in South Korea (2018-2020), we achieved a serotyping success rate of 97.10% (268/276), significantly outperforming conventional methods such as mAb and mPCR, which identified only 76.45% (211/276) of isolates. Whole-genome sequencing of the remaining eight non-typeable isolates revealed them to be non-pneumococcal (oral streptococci), confirming 100% accuracy for S. pneumoniae serotyping. Importantly, our method identified emerging and underrepresented serotypes, including serotype 13 and null capsule clade strains. nCATSerotyping offers a rapid, accurate, and comprehensive solution for pneumococcal serotyping, with significant advantages in identifying novel and non-typeable strains. This scalable platform will be a valuable tool for global serotype surveillance and next-generation multivalent pneumococcal vaccine development.IMPORTANCEAccurate pneumococcal serotyping is critical for vaccine development and epidemiological surveillance, particularly as non-vaccine serotypes emerge following widespread pneumococcal conjugate vaccine implementation. Current serotyping methods face significant limitations in coverage and accuracy, identifying around 76% of pneumococcal isolates and failing to detect emerging serotypes like serotype 13 and null capsule clades. The nanopore Cas9-targeted serotyping platform addresses these critical gaps by achieving 100% serotyping accuracy for confirmed Streptococcus pneumoniae isolates while identifying previously undetectable strains that conventional methods missed. This comprehensive approach is essential for monitoring vaccine effectiveness, understanding serotype replacement patterns, and informing next-generation vaccine development strategies. Furthermore, the identification of misclassified oral streptococci highlights the diagnostic precision needed for accurate pneumococcal surveillance, ensuring that epidemiological data accurately reflect true pneumococcal disease burden and serotype distribution patterns.
- New
- Research Article
- 10.1016/j.ijid.2025.108360
- Dec 28, 2025
- International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- Melvilí Cintrón + 9 more
Pneumococcal Serotype Distribution and Outcomes in Cancer Patients with Community-Acquired Pneumonia: A Prospective Study Using the 15-Valent Pneumococcal Conjugate Vaccine Serotype Specific Urinary Antigen Detection Assay.
- Research Article
- 10.3390/vaccines14010003
- Dec 19, 2025
- Vaccines
- Laura L Hammitt + 16 more
Background/Objectives: American Indian/Alaska Native individuals exhibit a higher prevalence of carriage of Streptococcus pneumoniae and are at increased risk of invasive pneumococcal disease compared with the general US population, driven by persistent inequities in health determinants. Although the use of pneumococcal vaccines has reduced carriage of vaccine serotypes, the prevalence of carriage of non-vaccine serotypes has increased. Methods: This study was a descriptive subgroup analysis of the PNEU-DAY study (NCT03547167; EudraCT 2017-004915-38). Safety, tolerability, and immunogenicity of sequential administration of either V114, a 15-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV (PCV13), followed 6 months later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), were evaluated in pneumococcal vaccine-naïve American Indian adults with or without pre-defined risk factors for pneumococcal disease. Polymerase chain reaction testing assessed nasopharyngeal/oropharyngeal carriage of S. pneumoniae. Results: Following administration of PCV and PPSV23, the proportions of participants with adverse events were generally comparable between vaccination groups. V114 and PCV13 were immunogenic for all respective vaccine serotypes, with V114 inducing robust immune responses to the two additional serotypes not included in PCV13 (22F and 33F), based on opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations at 30 days post-vaccination. Sequential administration with PPSV23 was immunogenic in both vaccination groups. Nasopharyngeal/oropharyngeal carriage of S. pneumoniae was observed in 16.7% to 22.6% of American Indian participants across the study timepoints. Conclusions: V114 was well tolerated and immunogenic for the 15 serotypes in V114 when administered either alone or followed by PPSV23. Use of V114 has the potential to expand serotype coverage and protect against pneumococcal disease resulting from serotypes absent in PCV13 among American Indian adults.
- Research Article
- 10.57187/s.4525
- Dec 17, 2025
- Swiss medical weekly
- Vasiliki Baroutsou + 3 more
The coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare systems worldwide, leading to concerns about reduced access to routine childhood immunisations. However, comprehensive data on how the pandemic specifically impacted paediatric vaccination coverage in Switzerland remain limited across the country. The present study provides an analysis of the timeliness and coverage of routine childhood immunisations in Switzerland before and during the COVID-19 pandemic, offering insights into potential fluctuations in coverage. To assess the impact of the COVID-19 pandemic on routine childhood immunisation in Switzerland by comparing vaccination coverage and timeliness for children under 35 months of age before and during the pandemic. Additionally, the study seeks to identify factors associated with the likelihood of children receiving vaccinations, considering demographic and geographic variables. We used 2019-2023 data from the Swiss National Vaccination Coverage Survey (SNVCS), a cross-sectional survey that collected immunisation information of children under 35 months of age from a nationally representative sample of households. Children who were eligible for a vaccine from March 2020 to March 2021 were considered as the COVID-affected group and those eligible for a vaccine before this date were included in the pre-COVID-19 cohort. Coverage of the following vaccine doses was considered: diphtheria at one, two and three doses (Di1, Di2, Di3); pneumococcus at one, two and three doses (PCV1, PCV2, PCV3); and measles first and second dose (MCV1, MCV2). Vaccine timeliness was defined as receiving a dose on time with a tolerance period of 30 days. We used logistic regression models to identify and understand the factors that might influence vaccination rates. For the diphtheria vaccines (Di1, Di2, Di3), while coverage remained high, there was a slight decrease observed in timely vaccination rates for some doses, with reductions of around 1% to 3% compared to pre-COVID-19 levels. The impact on PCV1, PCV2 and PCV3 showed similar trends, with slight reductions in coverage during the pandemic, but these differences were not statistically significant. For measles-containing vaccines (MCV1 and MCV2), coverage during the pandemic was higher compared to pre-COVID-19 rates. Geographic and demographic factors, such as an urban setting, nationality and linguistic region, significantly influence childhood vaccination rates in Switzerland. While minor declines in vaccine timeliness were observed (diphtheria vaccine, pneumococcal conjugate vaccine), the overall likelihood of vaccination was not significantly affected by the COVID-19 pandemic. However, changes in vaccination recommendations introduced in 2019 may have influenced these trends.
- Research Article
- 10.3390/vaccines13121246
- Dec 15, 2025
- Vaccines
- Aquino Albino Nhantumbo + 16 more
Background: Mozambique introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 using a three-dose primary series with no booster dose (3p+0) and later switched to the PCV13 using a schedule of two primary doses with one booster (2p+1). We aimed to describe the burden and serotype distribution of pneumococcal meningitis in children under 5 years of age in Mozambique over an eleven-year period starting with the year of PCV10 introduction, and assess the impact of the PCV vaccine and schedule changes. Methods: We analysed meningitis surveillance data in Mozambique from March 2013 through to December 2023. Cerebrospinal fluid (CSF) samples were collected from eligible children in three referral hospitals (Maputo Central Hospital [south], Beira Central Hospital [central], and Nampula Central Hospital [north]). Culture and polymerase chain reaction assay (qPCR) were performed on each sample. S. pneumoniae-positive samples were subsequently serotyped using multiplex assay. We estimated annual incidence rates for pneumococcal meningitis in children under 5 years old following the PCVs’ introduction (2013–2023). The impact of the product switch and schedule change from PCV10/3p+0 to PCV13/2p+1 on the burden and serotype distribution of pneumococcal meningitis was assessed. Results: Of the 4075 CSF samples tested, 7.4% (301/4075) were positive for S. pneumoniae, 2.5% (103/4075) for H. influenzae, and 1.0% (42/4075) for N. meningitidis. Pneumococcal meningitis incidence in children under five reduced from 44.7 cases per 100,000 in 2013 to 4.6 cases per 100,000 in 2023, an 89.7% reduction. In the PCV13/2p+1 period (2020–2023), pneumococcal meningitis incidence was 51.2% lower than the PCV10/3p+0 period (2013–2017) (IRR 0.49, 95% CI 0.4–0.6; p < 0.001). PCV10-serotype pneumococcal meningitis incidence among children under five decreased by 65.6% in the PCV13/2p+1 period (IRR 0.34, 95% CI 0.2–0.6; p < 0.001). We detected zero cases of pneumococcal meningitis due to the PCV13-serotype in 2020–2023, whereas non-PCV10/13-serotypes increased by 76% (IRR 1.76, 95% CI 1.2–2.6; p = 0.004). The case–fatality proportion decreased by 71.9% (95% CI 62.9–84.8%) in the PCV13/2p+1 period. Conclusions: Since the introduction of PCVs in Mozambique, the burden of pneumococcal meningitis and deaths in children under 5 years of age has substantially decreased, as well as the prevalence of PCV13-serotypes. Higher valency PCVs are needed due to the increased prevalence of non-PCV10/13-serotypes. Funding: Gavi, The Vaccine Alliance, reference number: MOZ-HSS-2-INS; WHO Reference: 2014405143-0, creation DFC to support HIB & Surveillance System.
- Research Article
- 10.1186/s12879-025-12328-w
- Dec 13, 2025
- BMC infectious diseases
- Claire Von Mollendorf + 23 more
Evaluating the effectiveness of the 13-valent pneumococcal conjugate vaccine and clinical and demographic characteristics on pneumococcal carriage density in young children in Papua New Guinea, Lao PDR, and Mongolia.
- Research Article
- 10.1099/jmm.0.002105
- Dec 12, 2025
- Journal of Medical Microbiology
- Satoshi Nakano + 9 more
Introduction.Streptococcus pneumoniae remains a major pathogen causing invasive diseases in children worldwide. Although pneumococcal conjugate vaccines (PCVs) have significantly reduced the disease burden, non-vaccine serotypes and antimicrobial resistance continue to be of concern.Hypothesis/ Gap Statement. The epidemiology of paediatric invasive pneumococcal disease (IPD) and antimicrobial resistance patterns in Japan following the coronavirus disease 2019 pandemic and prior to the introduction of PCV15 and PCV20 has not been fully characterized.Aim. To investigate the recent distribution of pneumococcal serotypes, antimicrobial susceptibility and genetic characteristics of isolates derived from paediatric patients in Japan from 2020 to 2023.Methodology. We conducted a nationwide, prospective surveillance study from March 2020 to April 2023. A total of 151 pneumococcal isolates (126 from IPD cases and 25 from non-IPD cases) were collected from children under 15 years of age. Serotyping, antimicrobial susceptibility testing and whole-genome sequencing were performed to assess epidemiological and genomic features.Results. No patient mortality was reported, but sequelae were observed in 4 (3.2%) of 125 IPD patients. The most common serotypes in IPD were 15B/C (23.0%), 15A (11.1%) and 24B (10.3%). Among 126 IPD isolates, the vaccine coverage rates for PCV13, 15 and 20 were 0.8, 13.5 and 42.1%, respectively. Overall resistance rates to penicillin (PEN), cefotaxime, meropenem (MEM) and erythromycin (ERY) were 31.8, 15.9, 18.5 and 88.7%, respectively. Serotypes 15A-CC63 and 35B-CC558 showed high resistance rates to β-lactams, including MEM. Genomic analysis revealed that the predominant genotypes were 15B/C-CC199, 15A-CC63, 24B-CC2754 and 10A-CC5236.Conclusion. Non-vaccine and PEN-, MEM- and ERY-resistant clones, particularly 15A-CC63 and 35B-CC558, were prevalent among paediatric pneumococci in Japan. Even with PCV20, less than half of the IPD isolates were covered; this underscores the need for ongoing genomic surveillance, antimicrobial stewardship and consideration of expanded-valency vaccines targeting additional serotypes, such as 15A and 35B.
- Research Article
- 10.3389/fimmu.2025.1707686
- Dec 12, 2025
- Frontiers in Immunology
- Taylor C Stevenson + 10 more
Streptococcus pneumoniae serotype-3 (ST-3) continues to be a major contributor to pneumococcal disease burden despite its inclusion in multivalent pneumococcal conjugate vaccines (PCV). Therefore, there is a pressing need to develop vaccines that can elicit more versatile immune responses against ST-3. To this purpose, our approach was to evaluate MAPS technology-based vaccine candidates in which biotinylated pneumococcal polysaccharides are non-covalently complexed with biotin-binding proteins. One such protein was SPP2, a fusion protein containing a nonhemolytic mutant of pneumolysin (Ply). The immunogenicity of SPP2 as a component of a vaccine candidate containing over 30 pneumococcal capsular polysaccharides, including ST-3 capsule (CPS3), was evaluated in rabbits. The vaccine demonstrated strong immunogenic properties, producing high titers of Ply-neutralizing antibodies and a robust opsonophagocytic antibody response to ST-3. A highly lethal ST-3 pneumococcal invasive disease model, in which antibodies to CPS3 alone are not highly protective, was developed to evaluate whether the inclusion of SPP2 can provide synergistic protection. Active immunization of mice with SPP2- and CPS3-containing vaccine and passive immunization of mice with antisera containing anti-CPS3 and anti-SPP2 antibodies conferred significant protection against death, whereas immunization against either antigen alone did not confer protection, suggesting a synergistic interaction between the protein- and polysaccharide-directed antibodies. These findings strongly support a vaccine approach that includes both pneumococcal polysaccharides and highly conserved disease-specific proteins to overcome the clinical resistance of ST-3 pneumococcal disease to traditional PCVs.