Pneumococcal Serotypes Research Articles

Surveillance of pneumococcal serotypes in adults hospitalised with acute lower respiratory tract infection in Bristol, UK

IntroductionPneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. MethodsA prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021–Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD−), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). ResultsOf 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD−; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9–80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD−, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DiscussionAmong adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

Serotype, antibiotic susceptibility and whole-genome characterization of Streptococcus pneumoniae in all age groups living in Southwest China during 2018-2022.

Streptococcus pneumoniae is a common pathogen that colonizes the human upper respiratory tract, causing high morbidity and mortality worldwide. This study aimed to investigate the prevalence status of S. pneumoniae isolated from patients of all ages in Southwest China, including serotype, antibiotic susceptibility and other molecular characteristics, to provide a basis for clinical antibiotic usage and vaccine development. This study was conducted from January 2018 to March 2022 at West China Hospital, West China Second University Hospital, First People's Hospital of Longquanyi District (West China Longquan Hospital), Meishan Women and Children's Hospital (Alliance Hospital of West China Second University Hospital) and Chengdu Jinjiang Hospital for Women and Children Health. Demographic and clinical characteristics of 263 pneumococcal disease (PD) all-age patients were collected and analyzed. The serotypes, sequence types (STs), and antibiotic resistance of the strains were determined by next-generation sequencing, sequence analysis and the microdilution broth method. The most common pneumococcal serotypes were 19F (17.87%), 19A (11.41%), 3 (8.75%), 23F (6.46%) and 6A (5.70%). Coverage rates for PCV10, PCV13, PCV15, PCV20 and PCV24 were 36.12, 61.98, 61.98, 63.12 and 64.26%, respectively. Prevalent STs were ST271 (12.55%), ST320 (11.79%), ST90 (4.18%), ST876 (4.18%) and ST11972 (3.42%). Penicillin-resistant S. pneumoniae (PRSP) accounted for 82.35 and 1.22% of meningitis and nonmeningitis PD cases, respectively. Resistance genes msrD (32.7%), mefA (32.7%), ermB (95.8%), tetM (97.3%) and catTC (7.6%) were found among 263 isolates. Most isolates showed high resistance to erythromycin (96.96%) and tetracycline (79.85%), with more than half being resistant to SXT (58.94%). A few isolates were resistant to AMX (9.89%), CTX (11.03%), MEN (9.13%), OFX (1.14%), LVX (1.14%) and MXF (0.38%). All isolates were susceptible to vancomycin and linezolid. Our study provides reliable information, including the prevalence, molecular characterization and antimicrobial resistance of S. pneumoniae isolates causing pneumococcal diseases in Southwest China. The findings contribute to informed and clinical policy decisions for prevention and treatment.

Validation and comprehensive analysis of Streptococcus pneumoniae IgG WHO enzyme-linked immunosorbent assay in an Indian reference laboratory.

Monitoring serotype-specific IgG levels againstpneumococci is crucial for assessing immunity, vaccine efficacy, and evaluating vaccination programs. The WHO ELISA for pneumococci is a standardized assay ensuring consistency in testing and comparability of results across laboratories. It involves a rigorous testing process to confirm accurate, precise and reliable detection of antibodies. We validated the protocol for 13 pneumococcal serotypes by assessing its specificity, reproducibility (coefficient of variation ≤15%), repeatability (coefficient of variation ≤20%), accuracy, lower limit of quantification, stability, and robustness. We found these parameters were within acceptable ranges and showed excellent performance. Our findings imply that the method employed is appropriate for evaluating 13 valent pneumococcal conjugate vaccine which is introduced in the national immunization program by comparing pre-and post-vaccination IgG response.

Changes in pneumococcal serotypes distribution and penicillin resistance in healthy children five years after generalization of PCV10

ObjectiveStreptococcus pneumoniae (S. pneumoniae) nasopharyngeal carriage has significantly decreased after the generalization of pneumococcal vaccination worldwide. This study sought to investigate changes in S. pneumoniae carriage rates, serotype distribution and penicillin non-susceptibility following the generalization of 10-valent pneumococcal conjugate vaccine. MethodsA prospective study was conducted in Marrakesh, Morocco, between 2017 and 2018, among healthy children attending vaccination centers. We collected nasopharyngeal swabs and questionnaire data for each child. Using univariate logistic regression, we analyzed the association between S. pneumoniae carriage and various risk factors. Comparisons of serotype diversity and penicillin resistance between 2017 and 2018 and the period before introduction of vaccination (2008–2009, n = 660) were performed using Simpson index and the chi-squared test, respectively. ResultsDuring 2017–2018, 515 children aged between 6 and 36 months participated. The S. pneumoniae carriage rate was 43.3%. Looking at the distribution serotypes, the rate of PCV10 serotypes rate was only 9.6%. Among non-vaccine serotypes, an increase in serotypes 6C/6D (22; 14%), 19B/19C (17; 10.8%), and 15B/15C (11; 7%) was observed. A particular increase in serotype diversity was also observed after the generalization of PCV10 (p < 0.001). S. pneumoniae non-susceptible to penicillin decreased, reaching a rate of 26.6% in 2017–2018. ConclusionThe significant change in S. pneumoniae carriage, serotype distribution, and penicillin resistance highlights the effectiveness of the pneumococcal conjugate vaccine among children in Marrakesh, Morocco.

Evidence of Reduced Virulence and Increased Colonization Among Pneumococcal Isolates of Serotype 3 Clade II Lineage in Mice.

Recent phylogenetic profiling of pneumococcal serotype 3 (Pn3) isolates revealed a dynamic interplay among major lineages with the emergence and global spread of a variant termed clade II. The cause of Pn3 clade II dissemination along with epidemiological and clinical ramifications are currently unknown. Here, we sought to explore biological characteristics of dominant Pn3 clades in a mouse model of pneumococcal invasive disease and carriage. Carriage and virulence potential were strain dependent with marked differences among clades. We found that clinical isolates from Pn3 clade II are less virulent and less invasive in mice compared to clade I isolates. We also observed that clade II isolates are carried for longer and at higher bacterial densities in mice compared to clade I isolates. Taken together, our data suggest that the epidemiological success of Pn3 clade II could be related to alterations in the pathogen's ability to cause invasive disease and to establish a robust carriage episode.

Whole-cell pneumococcal vaccines: a future-proof approach to overcoming pneumococcal serotype replacement

Whole-cell pneumococcal vaccines: a future-proof approach to overcoming pneumococcal serotype replacement

Otitis media: recent advances in otitis media vaccine development and model systems.

Otitis media is an inflammatory disorder of the middle ear caused by airways-associated bacterial or viral infections. It is one of the most common childhood infections as globally more than 80% of children are diagnosed with acute otitis media by 3 years of age and it is a common reason for doctor's visits, antibiotics prescriptions, and surgery among children. Otitis media is a multifactorial disease with various genetic, immunologic, infectious, and environmental factors predisposing children to develop ear infections. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common culprits responsible for acute otitis media. Despite the massive global disease burden, the pathogenesis of otitis media is still unclear and requires extensive future research. Antibiotics are the preferred treatment to cure middle ear infections, however, the antimicrobial resistance rate of common middle ear pathogens has increased considerably over the years. At present, pneumococcal and influenza vaccines are administered as a preventive measure against otitis media, nevertheless, these vaccines are only beneficial in preventing carriage and/or disease caused by vaccine serotypes. Otitis media caused by non-vaccine serotype pneumococci, non-typeable H. influenza, and M. catarrhalis remain an important healthcare burden. The development of multi-species vaccines is an arduous process but is required to reduce the global burden of this disease. Many novel vaccines against S. pneumoniae, non-typeable H. influenza, and M. catarrhalis are in preclinical trials. It is anticipated that these vaccines will lower the disease burden and provide better protection against otitis media. To study disease pathology the rat, mouse, and chinchilla are commonly used to induce experimental acute otitis media to test new therapeutics, including antibiotics and vaccines. Each of these models has its advantages and disadvantages, yet there is still a need to develop an improved animal model providing a better correlated mechanistic understanding of human middle ear infections, thereby underpinning the development of more effective otitis media therapeutics. This review provides an updated summary of current vaccines against otitis media, various animal models of otitis media, their limitations, and some future insights in this field providing a springboard in the development of new animal models and novel vaccines for otitis media.

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China

BackgroundThe thirteen-valent pneumococcal conjugate vaccine (PCV13) is not included in the national immunization program and is administered voluntarily with informed consent in China. In preparation for assessing the impact of pilot introduction in Hainan Province, we conducted a carriage study among children under 5 years of age from four locations in Hainan Province, China.MethodsFrom March to June 2022, nasopharyngeal (NP) swabs, collected from healthy children aged younger than 59 months who lived in the 4 different locations (Haikou, Wanning, Baisha and Qiongzhong) in Hainan Province, were tested for pneumococcus using conventional culture. Pneumococcal isolates were serotyped using the Quellung reaction. Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age, daycare attendance and other factors.ResultsPneumococcus was isolated in 710 (30.4%) of the 2333 children enrolled. Of 737 pneumococci, 29 serotypes were identified; 60.9% were PCV13 serotypes; the most common vaccine serotypes were 6B (20.4%), 19F (13.0%), 6A (11.9%) and 23F (6.1%); and the most common nonvaccine serotypes were 23A (12.9%), 34 (6.1%) and nontypeable (NT) pneumococci (5.6%). Children vaccinated with PCV13 had lower carriage (17.7% vs 32.5%; P = 0.0001) and fewer PCV13 serotypes (41.9% vs 62.7%; P = 0.0017) compared to unimmunized children. After adjustment, NP carriage was higher among children attending daycare (aOR = 2.3, 95% CI: 1.7–3.2), living in rural areas (aOR = 1.4, 95% CI: 1.1–1.8), living with siblings (aOR = 1.3, 95% CI: 1.0–1.6) and whose mothers had completed senior high/technical secondary school (aOR = 1.5, 95% CI: 1.1–2.0). In contrast, completion of 3–4 doses of PCV13 were associated with a lower carriage rate (aOR = 0.6, 95% CI: 0.4–0.9).ConclusionsWe established the baseline of pneumococcal carriage, serotype distribution and PCV13 immunization rates among healthy children under 5 years of age in Hainan Province, prior to the introduction of PCV13 into the national immunization program. The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.Graphical

Impact of age on pneumococcal colonization of the nasopharynx and oral cavity: an ecological perspective.

Pneumococcal carriage studies have suggested that pneumococcal colonization in adults is largely limited to the oral cavity and oropharynx. In this study, we used total abundance-based β-diversity (dissimilarity) and β-diversity components to characterize age-related differences in pneumococcal serotype composition of respiratory samples. quantitative PCR (qPCR) was applied to detect pneumococcal serotypes in nasopharyngeal samples collected from 946 toddlers and 602 adults, saliva samples collected from a subset of 653 toddlers, and saliva and oropharyngeal samples collected from a subset of 318 adults. Bacterial culture rates from nasopharyngeal samples were used to characterize age-related differences in rates of colonizing bacteria. Dissimilarity in pneumococcal serotype composition was low among saliva and nasopharyngeal samples from children. In contrast, respiratory samples from adults exhibited high serotype dissimilarity, which predominantly consisted of abundance gradients and was associated with reduced nasopharyngeal colonization. Age-related serotype dissimilarity was high among nasopharyngeal samples and relatively low for saliva samples. Reduced nasopharyngeal colonization by pneumococcal serotypes coincided with significantly reduced Moraxella catarrhalis and Haemophilus influenzae and increased Staphylococcus aureus nasopharyngeal colonization rates among adults. Findings from this study suggest that within-host environmental conditions, utilized in the upper airways by pneumococcus and other bacteria, undergo age-related changes. It may result in a host-driven ecological succession of bacterial species colonizing the nasopharynx and lead to competitive exclusion of pneumococcus from the nasopharynx but not from the oral habitat. This explains the poor performance of nasopharyngeal samples for pneumococcal carriage among adults and indicates that in adults saliva more accurately represents the epidemiology of pneumococcal carriage than nasopharyngeal samples.

What do you get? Transmission of pneumococcal pneumonia.

Streptococcus pneumoniae is a polysaccharide encapsulated bacterium responsible for the majority of cases of community acquired pneumonia. The upper respiratory tract of children becomes colonized with pneumococci early in life, from the first weeks of life up to 18 months. Factors which influence timing of colonization include geographical localization, socio-economic circumstances, and household conditions. Pneumococcal pneumonia to a degree is a seasonal disease, peaking in the winter months. One of the epidemiological determinants is that viral infections (in particular influenza) predispose for pneumococcal pneumonia. The infectious nature of pneumococcal pneumonia was underscored during the COVID-19 pandemic. Due to societal restrictions imposed (face masks, social distancing) the incidence of invasive pneumococcal disease (IPD) dropped, and returned to pre-COVID-19 numbers after lifting of the restrictions. There are 100 different S. pneumoniae serotypes, based on differences in the capsular polysaccharide. Introduction of protein conjugated polysaccharide vaccines (PCV) has reduced the incidence of IPD in children. Because children are the reservoir for other risk groups, in particular the elderly, introduction of PCV has indirectly also reduced the burden of IPD in latter risk group. The first generation of PCV consisted of the seven most prevalent pneumococcal serotypes. After implementation, replacement colonization of the upper respiratory tract with non-vaccine serotypes was observed and also replacement disease. Upcoming 24-valent PCVs will have a much broader coverage, but whether replacement disease now has been eliminated remains to be seen.

Emerging pneumococcal serotypes in Iraq: scope for improved vaccine development.

Pneumococcal disease is a global public health concern as it affects the young, aged and the immunocompromised. The development of pneumococcal vaccines and their incorporation in the immunization programs has helped to reduce the global burden of disease. However, serotype replacement and the emergence of non-vaccine serotypes as well as the persistence of a few vaccine serotypes underscores the need for development of new and effective vaccines against such pneumococcal serotypes. In the Middle East, places of religious mass gatherings are a hotspot for disease transmission in addition to the global risk factors. Therefore, the periodic surveillance of pneumococcal serotypes circulating in the region to determine the effectiveness of existing prevention strategies and develop improved vaccines is warranted. Currently, there is a lack of serotype prevalence data for Iraq due to inadequate surveillance in the region. Thus, this review aims to determine the pneumococcal serotypes circulating in Iraq which may help in the development and introduction of improved pneumococcal vaccines in the country.

Characteristics of Streptococcus pneumoniae strains serotype 19A isolated from children in Moscow during the post-vaccination period (2015–2022)

Introduction. Community-acquired pneumonia (CAP) is a leading cause of children mortality and morbidity worldwide. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) had a very good effect on the CAP prevalence. However, serotype 19A remains the leading cause of severe pneumococcal disease in both vaccinated and unvaccinated children. &#x0D; The purpose of the work. To analyze the clonal epidemiology and sensitivity to antibacterial drugs of pneumococcus serotype 19A strains in the post-vaccination period for monitoring and control of vaccination.&#x0D; Materials and methods. The study included twenty six isolates of pneumococci serotype 19A isolated in children in Moscow between 2015 and 2022. Serotyping was carried out using the Neufeld capsule swelling test. Sensitivity was determined using the microdilution method. Resistance genes and multilocus sequence typing was performed using the PCR method.&#x0D; Results. By 2019–2022 the detection rate of serotype 19A decreased from 61.5% to 38.5%. A total of 12 different sequence types were identified. Most isolates belonged to 2 clonal complexes: CC230 (n = 15), CC320 (n = 6). Sixteen isolates exhibited a multidrug resistance phenotype (MDR). The dominant phenotype was extremely drug-resistant in the combination of β/Eri/Cli/TMP/Tet (43.8%). The most of MDR isolates belonged to clonal complexes: CC230 (8/16), CC320 (6/16) and Singleton 16988 (12.5%).&#x0D; Conclusion. After the introduction of PCV13, the prevalence of serotype 19A decreased, but MDR isolates of this serotype continued to increase. These results highlight the need for continued monitoring of the pneumococcal population exhibiting high resistance to reduce the risk of severe disease caused by this organism.

Pneumococcal serotypes and risk factors in adult community acquired pneumonia 2018–20: a multicentre UK cohort study

BackgroundHigher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. MethodsWe conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. FindingsOf 1921 adults hospitalised with CAP, 781 (40·7%, 95% confidence intervals (CI) 38·5-42·9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31·0%, 95% CI 27·8-34·3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70·7%, 95% CI 64·5-76·0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2·8-5·6%), and PCV20-non13-serotypes in 192 (24·6%), with serotype 8 most prevalent (123/192, 64·1%, 95% CI 57·1-70·5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p<0·001) and less likely to be male (44% versus 61%, p=0·01). PPV23-non13-serotypes were found in 252 (32·3%, 95% CI 29·1-35·6%) pneumococcal CAP patients. InterpretationDespite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. FundingUnrestricted investigator-initiated research grant from Pfizer; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

Streptococcus pneumoniae serotype 33G: genetic, serological, and structural analysis of a new capsule type.

Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen with the greatest burden of disease in Asia and Africa. The pneumococcal capsular polysaccharide has biological relevance as a major virulence factor as well as public health importance as it is the target for currently licensed vaccines. These vaccines have limited valency, covering up to 23 of the >100 known capsular types (serotypes) with higher valency vaccines in development. Here, we have characterized a new pneumococcal serotype, which we have named 33G. We detected serotype 33G in nasopharyngeal swabs (n = 20) from children and adults hospitalized with pneumonia, as well as healthy children in Mongolia. We show that the genetic, serological, and biochemical properties of 33G differ from existing serotypes, satisfying the criteria to be designated as a new serotype. Future studies should focus on the geographical distribution of 33G and any changes in prevalence following vaccine introduction.

Nanofluidic qPCR unable to detect and serotype Streptococcus pneumoniae in urine samples of hospitalized South African patients with community-acquired pneumonia

Pneumonia is a major cause of death among adults living with HIV in South Africa, but the etiology of many cases remains unknown. This study evaluated the utility of a nanofluidic qPCR assay to detect and serotype Streptococcus pneumoniae in urine samples from patients hospitalized with community-acquired pneumonia (CAP). The nanofluidic qPCR assay was optimized to target 13 pneumococcal serotypes and 4 reference genes. Archived urine samples collected from patients > 15 years of age hospitalized with pneumonia between April 2018 and August 2019 were retrospectively tested using the nanofluidic qPCR assay, BinaxNOW urine antigen test, and standard LytA qPCR. Blood culture was undertaken on a subset of the samples at the discretion of the attending physician. Cohens' Kappa statistics were used to determine the concordance between the methods. Of the 828 adults hospitalized for CAP, urine samples were available in 53% (n = 439). Of those, a random subset of 96 (22%) samples underwent testing. Of the participants included in the final analysis, the mean age was 45.8 years (SD 16.2), 49% (n = 47) were female, 98% (n = 94) were black, and 66% (n = 63) were living with HIV infection. The nanofluidic qPCR method was able to detect PCV13 vaccine strains spiked into urine samples; however, the method failed to detect any pneumococcus in clinical samples. In comparison, 19% of the pneumonia cases were attributed to S. pneumoniae using urine antigen testing. Nanofluidic qPCR is unable to detect and serotype Streptococcus pneumoniae in urine samples of South Africans hospitalized with CAP.

Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci

BackgroundAlthough vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques.MethodsC57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia.ResultsSerum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection.ConclusionsPrime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.

Pneumococcal Polysaccharide Conjugated Vaccines and the Problem of Changing Circulating Serotypes of Pneumococcus

Relevance. In 2007, WHO recommended pneumococcal conjugate vaccines (PCV) be included in national immunization schedules for young children. By 2020, 145 countries, including Russia, were using PCV. Aims. To identify vaccines with high epidemiological and immunological efficacy against various forms of pneumococcal infection, including carriage. Conclusions. It has been shown that PCV has high epidemiological and immunological efficacy against various forms of pneumococcal infection, including carriage. It was revealed that the mass use of PCV, leading to the elimination of "vaccine" serotypes, is simultaneously accompanied by the spread of cases of infection due to serotypes not included in vaccines, which significantly reduces the positive effect of vaccination. This requires frequent replacement of serotype polysaccharides in the vaccine in accordance with the serotypes of circulating strains. An alternative to PCV can be vaccines based on pneumolysin, surface pneumococcal proteins, whole – cell and live attenuated, protein-based subunit vaccines, etc. vaccine variants.

Determination of Pneumococcal Serotypes by Sequetyping and Sequential Conventional Multiplex PCR in the Vaccine Era

Pneumococcal serotyping is required for epidemiological surveillance to guide vaccination strategy. DNA-based approaches are more affordable, but the combination of sequetyping and sequential conventional multiplex polymerase chain reaction (cmPCR) may complement one another. A total of 101 isolates were subjected to sequetyping and sequential cmPCR following previously published protocols, and the outputs were compared. The sequetyping method determined up to the serotype level for 99 isolates (98%). On the other hand, the sequential cmPCR technique identified 91 isolates (90.1%), with 63 of them (62.4%) up to the serotype level. Sequetyping generated discrete serotypes for 6A/B, 11A/D, 15A/F, and 15B/C as 6A (n = 11), 6B (n = 10), 11A (n = 5), 15C (n = 1), and 15A (n = 1). In conclusion, the cpsB gene sequetyping method produced a comparable output with sequential cmPCR, further discriminating some sub-serogroups among the isolate collection.

Vaccination against Streptococcus pneumoniae in Children Born between 2015 and 2018 in Poland-How Has the Introduction of Free Compulsory Pneumococcal Vaccination Affected Its Uptake?

Starting from 2017, pneumococcal vaccination was added to the Polish vaccination calendar as mandatory for all children born after 2016. The 10-valent conjugate vaccine was selected as mandatory and therefore free of charge. This paper aims to examine the impact of introducing mandatory vaccination on vaccine uptake. For this purpose, an analysis was conducted for 1595 vaccination record sheets from outpatient clinics in Wrocław and surrounding villages for children born 2015-2018. After the introduction of compulsory vaccination, the percentage of children fully vaccinated against pneumococcus increased (60.4% vs. 84.8%, p < 0.001). A significant decrease in the number of children who did not receive any dose of the vaccine was observed (27.8% to 3.3%, p < 0.001). The introduction of compulsory vaccination did not affect the completion of the pneumococcal schedule (11.8% vs. 11.9%). Compulsory PCV10 vaccination resulted in the less frequent choice of the 13-valent vaccine (72.3% vs. 19.9%, p < 0.001). More children in rural outpatient clinics were vaccinated against pneumococcus compared to urban outpatient clinics (84.8% vs. 70.8%, p < 0.001). The introduction of free pneumococcal vaccination increased the proportion of children vaccinated, although it did not affect the rate of discontinuation of the initiated schedule. In Poland, the increased popularity of the 10-valent vaccine at the expense of the 13-valent one translated into a change in the proportion of pneumococcal serotypes causing invasive pneumococcal disease.