PCV13 Vaccination Research Articles

Streptococcus pneumoniae serotype distribution in Bangladeshi under-fives with community-acquired pneumonia pre-10-valent pneumococcal conjugate vaccination

BackgroundStreptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced.MethodsA total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response.ResultsS. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406).ConclusionsIn almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine.

Poststreptococcal acute glomerulonephritis with 22F pneumococcal bacteremia.

Pneumococcal vaccines have been available worldwide since the early 2000s; consequently, few reports exist of poststreptococcal acute glomerulonephritis (PSAGN) or complications of pneumococcal infection. We describe a patient with PSAGN and bacteremia with Streptococcus pneumoniae serotype 22F (not covered by the 13-valent pneumococcal vaccine (PCV 13)). A 5-year-old boy received the PCV13 vaccine and was admitted to our hospital with a fever and gross hematuria. A throat swab was positive for a streptococcal antigen, and his serum anti-streptolysin O and creatinine levels were increased. Low serum C3 levels suggested PSAGN, with an infiltrating shadow on chest X-ray. His blood culture isolated S. pneumoniae serotype 22F, and he was administered intravenous ceftriaxone for 10days. His kidney function, pneumonia, and bacteremia improved. Children with PSAGN should be evaluated for pneumococcal bacteremia due to strains not covered by the vaccine.

Prediction of post-PCV13 pneumococcal evolution using invasive disease data enhanced by inverse-invasiveness weighting.

After introducing pneumococcal conjugate vaccines (PCVs), serotype replacement occurred in Streptococcus pneumoniae. Predicting which pneumococcal strains will become common in carriage after vaccination can enhance vaccine design, public health interventions, and understanding of pneumococcal evolution. Invasive pneumococcal isolates were collected during 1998-2018 by the Active Bacterial Core surveillance (ABCs). Carriage data from Massachusetts (MA) and Southwest United States were used to calculate weights. Using pre-vaccine data, serotype-specific inverse-invasiveness weights were defined as the ratio of the proportion of the serotype in carriage to the proportion in invasive data. Genomic data were processed under bioinformatic pipelines to define genetically similar sequence clusters (i.e., strains), and accessory genes (COGs) present in 5-95% of isolates. Weights were applied to adjust observed strain proportions and COG frequencies. The negative frequency-dependent selection (NFDS) model predicted strain proportions by calculating the post-vaccine strain composition in the weighted invasive disease population that would best match pre-vaccine COG frequencies. Inverse-invasiveness weighting increased the correlation of COG frequencies between invasive and carriage data in linear or logit scale for pre-vaccine, post-PCV7, and post-PCV13; and between different epochs in the invasive data. Weighting the invasive data significantly improved the NFDS model's accuracy in predicting strain proportions in the carriage population in the post-PCV13 epoch, with the adjusted R2 increasing from 0.254 before weighting to 0.545 after weighting. The weighting system adjusted invasive disease data to better represent the pneumococcal carriage population, allowing the NFDS mechanism to predict strain proportions in carriage in the post-PCV13 epoch. Our methods enrich the value of genomic sequences from invasive disease surveillance.IMPORTANCEStreptococcus pneumoniae, a common colonizer in the human nasopharynx, can cause invasive diseases including pneumonia, bacteremia, and meningitis mostly in children under 5 years or older adults. The PCV7 was introduced in 2000 in the United States within the pediatric population to prevent disease and reduce deaths, followed by PCV13 in 2010, PCV15 in 2022, and PCV20 in 2023. After the removal of vaccine serotypes, the prevalence of carriage remained stable as the vacated pediatric ecological niche was filled with certain non-vaccine serotypes. Predicting which pneumococcal clones, and which serotypes, will be most successful in colonization after vaccination can enhance vaccine design and public health interventions, while also improving our understanding of pneumococcal evolution. While carriage data, which are collected from the pneumococcal population that is competing to colonize and transmit, are most directly relevant to evolutionary studies, invasive disease data are often more plentiful. Previously, evolutionary models based on negative frequency-dependent selection (NFDS) on the accessory genome were shown to predict which non-vaccine strains and serotypes were most successful in colonization following the introduction of PCV7. Here, we show that an inverse-invasiveness weighting system applied to invasive disease surveillance data allows the NFDS model to predict strain proportions in the projected carriage population in the post-PCV13/pre-PCV15 and pre-PCV20 epoch. The significance of our research lies in using a sample of invasive disease surveillance data to extend the use of NFDS as an evolutionary mechanism to predict post-PCV13 population dynamics. This has shown that we can correct for biased sampling that arises from differences in virulence and can enrich the value of genomic data from disease surveillance and advance our understanding of how NFDS impacts carriage population dynamics after both PCV7 and PCV13 vaccination.

Impact of PCV13 and PPSV23 Vaccination on Invasive Pneumococcal Disease in Adults with Treated Rheumatoid Arthritis: A Population-Based Study

On-time receipt of pneumococcal vaccines is essential in patients with rheumatoid arthritis (RA) as immunosuppressive medications increase their risk of invasive pneumococcal disease (IPD). However, data regarding the impact of timely administration of these vaccines on the risk of developing IPD are lacking for RA patients. We conducted a retrospective cohort study to assess the impact of on-time vaccination for pneumococcal conjugate vaccine (PCV) 13 and pneumococcal polysaccharide vaccine (PPSV) 23 in patients treated for RA on the development of IPD using national Veterans Affairs data from 2010 to 2018. Patients &gt; 18 years of age, diagnosed with RA, and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. A total of 33,545 patients were included in the cohort. Non-compliance with PCV recommendations was associated with an increased risk of IPD in a multivariable logistic regression model. This finding was consistent whether IPD status was ascertained by International Classification of Diseases coding (OR 2.42, 95%CI 2.14–2.73) or microbiologic data (OR 1.64, 95%CI 1.26–2.14). Providers should actively seek opportunities to provide pneumococcal vaccinations to patients with RA, as their on-time administration is associated with a decreased risk of IPD.

Pneumococcal Serotype-Specific Antibodies in Children with Recurrent Oto-sinopulmonary Infections.

Low titers to pneumococcal vaccine are a frequent finding in pediatric patients with recurrent oto-sinopulmonary infections. To characterize the pre- and post-immunization antibody trend for each serotype included in the pneumococcal 13-valent conjugate vaccine (PCV13), in a cohort of pediatric patients with recurrent oto-sinopulmonary infections. This retrospective review identified 182 patients with recurrent oto-sinopulmonary infections (131 required an immune workup and 99 had low pneumococcal titers leading to a PCV13 vaccine booster). Baseline pneumococcal serotype-specific antibody titers at initial visit and 6 weeks after the vaccine booster were obtained. An adequate response to the pneumococcal conjugate vaccine was deemed to be a 4-fold increase over baseline and/or a post-immunization titer of 1.3 µg/ml or greater. Overall, PCV13 booster provided a significant improvement in the number of protective titers, increasing from 3.6 serotypes at baseline to 11.1 serotypes at 6 weeks (p < 0.001). This increase correlated with improved clinical outcomes (81% showed no signs of recurrent infection after the first booster and 94% after a second booster). Post-immunization antibody concentrations were significantly higher than at baseline for all serotypes (p< 0.05) and only 8, 9N, and 12F did not exhibit a greater than 4-fold increase (p> 0.05) 6 weeks following booster. There were no differences between patients at different ages in post-immunization titer levels for all serotypes. In pediatric patients with recurrent oto-sinopulmonary infections, an additional pneumococcal booster proved to be effective in the protection of these children against further infections, across all age groups.

Carriage of Streptococcus pneumoniae in adults hospitalised with community-acquired pneumonia

We aimed to determine the prevalence of and risk factors for nasopharyngeal and oral pneumococcal carriage in adults with community-acquired pneumonia (CAP), and the relationship between carried and disease-causing serotypes. Between 2016 and 2018, nasopharyngeal swabs, oral-fluid, and urine were collected from hospitalised adults recruited into a prospective cohort study of CAP. Pneumococcal carriage was detected by semi-quantitative real-time PCR of direct and culture-enriched nasopharyngeal swabs and culture-enriched oral-fluid. LytA and piaB positive/indeterminate samples underwent semi-quantitative serotype/serogroup-specific real-time-PCR. Serotypes in urine were identified using a 24-valent serotype-specific urinary-antigen assay. We included 465 CAP patients. Nasopharyngeal carriage was detected in 34/103 (33.0%) swabbed pneumococcal pneumonia patients and oral carriage in 18/155 (12%) of sampled pneumococcal pneumonia patients. Concordance between nasopharyngeal/urine serotypes and oral/urine serotypes was 70.6% and 50% respectively. Serotypes 3 (26%, 22.2%), 8 (19.7%, 19.4%), non-typeable (11.6%, 13.9%) and 19A/F (7.5%, 8.3%) were most prevalent in urine and nasopharyngeal swabs respectively, with non-typeable (35%) and 15A/F (17%) most prevalent in oral-fluid. Pneumococcal carriage was significantly associated with pneumococcal pneumonia (nasopharyngeal adjusted odds ratio [aOR] 8.1, 95% confidence interval [CI] 3.8-17.2; oral aOR 5.5, 95% CI 2.1-13.3). All-cause CAP patients ≥65 years had lower odds of nasopharyngeal carriage (aOR 0.47, 95% CI 0.24-0.91) and current smokers had higher odds of oral carriage (aOR 2.69, 95% CI 1.10-6.60). The association between nasopharyngeal carriage and pneumococcal CAP was strong. Adult carriage and disease from serotypes 8 and 19A may support direct protection of adults with PCV vaccines.

Study of pediatric invasive pneumococcal disease in the 13-pneumococcal conjugated vaccine era

BackgroundInvasive pneumococcal disease (IPD) remains a significant concern among children under 5, despite vaccination efforts. This study assessed IPD prevalence and associated risks in pediatric population. MethodsAn observational, retrospective, multicenter study in Comunidad Valenciana, Spain, of IPD cases in children under 13 from January 2012 to September 2022. Data from the CV Microbiology Surveillance Network (RedMIVA) and medical records were reviewed. ResultsA total of 379 IPD cases in 377 patients were analyzed, predominantly males (54.11 %) under 5 (81.17 %). PCV13 vaccination notably reduced PCV13-serotypes IPD (p=0.0002), except serotype 3. Pneumonia was common, with half having underlying conditions (50.40 %). Worse outcomes occurred in patients with neurological disorders (ANOVA, p=0.57). Vaccine failures often involved underlying conditions (63 %) and serotypes 3 and 19A. Immunodeficiencies may relate to recurrent IPD, but evidence is limited. ConclusionDespite vaccination, IPD still impacts children, influenced by immunological status, affecting severity and mortality.

Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study

Background13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13...

Multiple vaccine comparison in the same adults reveals vaccine-specific and age-related humoral response patterns: an open phase IV trial

Vaccine responsiveness is often reduced in older adults. Yet, our lack of understanding of low vaccine responsiveness hampers the development of effective vaccination strategies to reduce the impact of infectious diseases in the ageing population. Young-adult (25–49 y), middle-aged (50-64 y) and older-adult ( ≥ 65 y) participants of the VITAL clinical trials (n = 315, age-range: 28-98 y), were vaccinated with an annual (2019–2020) quadrivalent influenza (QIV) booster vaccine, followed by a primary 13-valent pneumococcal-conjugate (PCV13) vaccine (summer/autumn 2020) and a primary series of two SARS-CoV-2 mRNA-1273 vaccines (spring 2021). This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the adult age-range. Booster QIV vaccination induced comparable H3N2 hemagglutination inhibition (HI) titers in all age groups, whereas primary PCV13 and mRNA-1273 vaccination induced lower antibody concentrations in older as compared to younger adults (primary endpoint). The persistence of humoral responses, towards the 6 months timepoint, was shorter in older adults for all vaccines (secondary endpoint). Interestingly, highly variable vaccine responder profiles overarching multiple vaccines were observed. Yet, approximately 10% of participants, mainly comprising of older male adults, were classified as low responders to multiple vaccines. This study aids the identification of risk groups for low vaccine responsiveness and hence supports targeted vaccination strategies. Trial number: NL69701.041.19, EudraCT: 2019-000836-24.

The effect of two circovirus vaccines on the safety and weight gain of pigs in the rearing and fattening groups

The aim of the work is to experimentally find out in comparison the effect of two vaccines against circovirus infection Porcilis PCV and Circovac on the safety and weight gain of pigs in the rearing and fattening groups in the pig holding. The object of the study were 6687 pigs: 3393 heads vaccinated according to the instructions with the Circovac vaccine at a dose of 0.5 ml (group 1), and 3294 heads vaccinated according to the instructions with the Porcilis PCV vaccine at a dosage of 2.0 ml (group 2). In both groups, vaccination was carried out on the day of weaning on the 27-28 day of life intramuscularly in the neck area. When weaning, when transferring to fattening and before slaughter, the animals were weighed. According to the results of weighing, the average weight of animals was determined at 28 days, at 75 days and the weight at sale, as well as the average daily gain during rearing and fattening. Autopsy was performed on 209 fallen piglets from group 1 and 202 fallen piglets from group 2. During the pathoanatomic examination, a complex of pathoanatomic changes characteristic of circovirus was not found in any piglet. After vaccination of pigs in two groups with vaccines during the periods of rearing and fattening, there were no cases of cirrhosis among the livestock of both groups. The difference in indicators of case, technological marriage, average weight at weaning, average weight at transfer to fattening, average daily weight gain and weight at realization in the studied groups is minimal, not significant. Circovac vaccine in a dose of 0.5 ml proved to be no worse than the Porcilis PCV vaccine in a dosage of 2.0 ml.

Hubungan Faktor Risiko Eksternal terhadap Kejadian Otitis Media Akut pada Balita di RS Aminah Ciledug

This study examined the correlation of external risk factors to the incidence of AOM in toddlers and preschoolers. This research used an observational analytic design with a cross-sectional approach and data processing uses univariate, bivariate and multivariate analysis. Of the 61 research subjects, the majority of toddlers with AOM were 1-3 years old, 32 children (52.5%), 33 children (54.1%) were female, 37 children (60.7%) had perforation stage. 52 children (85.2%) received exclusive breastfeeding. The results showed that the four variables, including breastfeeding duration, use of pacifiers, PCV vaccinations, and history of ARI (Acute Respiratory Infection), correlated to incidences of acute otitis media. PCV vaccination and history of ARI are the most influencing variables with p-values of 0.024 and 0.006. There is a relationship between external risk factors and the incidence of AOM in toddlers, where the most influential variables are the administration of the PCV vaccine and a history of upper respiratory infection. The researcher of this study suggests at least three doses of PCV vaccination for children at the ages 2, 4, and 6 months, alongside the protection from triggers of ARI to prevent the occurrence of AOM.

Pneumococcal vaccination effectiveness (PCV13 and PPSV23) in individuals with and without reduced kidney function: a test-negative design study.

Streptococcus pneumoniae vaccination effectiveness (VE) in individuals with reduced kidney function is unknown. We estimated pneumococcal conjugate vaccine (PCV13), pneumococcal polysaccharide vaccine (PPSV23), and combined PCV13 and PPSV23 effectiveness against pneumococcal disease in individuals with and without reduced estimated glomerular filtration rate (eGFR). All eligible individuals (case and controls) were adults (aged ≥18 years) hospitalized within the Geisinger Health System and required to have S. pneumoniae urinary antigen testing (i.e. test-negative design). Vaccination records were obtained from the electronic health record and statewide vaccination registry. After controlling for the probability of receiving a pneumococcal vaccine, we used multivariable logistic regression models to estimate the odds ratios (ORs) of vaccination between those who did and did not meet the S. pneumoniae case definition. VE was calculated as (1-OR)×100%. There were 180 cases and 3889 controls (mean age 69 years, female 48%, white 97%, mean eGFR 71mL/min/1.73m2). The adjusted population PCV13 VE was 39% (95% CI 13%-58%), and combination PCV13 and PPSV23 was 39% (95% CI 12%-58%). PPSV23 VE was -3.7% (95% CI -57% to 32%). Stratified by eGFR, adjusted PCV13 VE was consistent in eGFR ≥60 [VE 38% (95% CI 2.9%-61%)] and 30-59 [VE 61% (95% CI 24%-80%)] without significant interaction. VE was not calculable for eGFR <30 due to small sample size. PCV13 vaccination was associated with reduced risk of S. pneumoniae hospitalization in individuals with a reduced eGFR (30-59mL/min/1.73m2).

Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14™) administered to 6–8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study

BackgroundIntroduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE’s 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13). MethodsThis is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6–8 weeks old healthy infants at 6–10–14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study. FindingsThe safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13. InterpretationsBE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine.The study was prospectively registered with clinical trial registry of India – CTRI/2020/02/023129.

Nasopharyngeal Carriage of Streptococcus pneumoniae in Tunisian Healthy under-Five Children during a Three-Year Survey Period (2020 to 2022).

We aimed to assess the prevalence of nasopharyngeal pneumococcal carriage and to determine serotype distribution, antibiotic susceptibility patterns, and evolutionary dynamics of Streptococcus pneumoniae isolates in healthy under-five children. Nasopharyngeal swabs were collected from healthy children over three survey periods between 2020 and 2022. All pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. A total of 309 S. pneumoniae isolates were collected, with an overall prevalence of nasopharyngeal pneumococcal carriage of 24.4% (CI95%: [22-26.8%]). These isolates were classified into 25 different serotypes. The most common serotypes were 14 (14.9%), 19F (12%), 6B (10.4%), and 23F (7.4%), which are covered by the PCV10 vaccine, as well as 19A (8.4%) and 6A (7.8%), which are covered by the PCV13 vaccine. A significant decrease in the proportion of serotype 19F (p = 0.001) and an increase in serotypes 19A (p = 0.034) and 6A (p = 0.029) were observed between the three survey periods. Multidrug resistance (MDR) was noted for 56.6% of the isolates. A significant association with antimicrobial resistance was observed for the most frequent serotypes, mainly serotype 19A. In conclusion, one-quarter of healthy under-five children in Tunisia carried S. pneumoniae in their nasopharynx. A dominance of vaccine serotypes significantly associated with antimicrobial resistance was recorded.

Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation

BackgroundPneumococcal carriage is the primary reservoir for transmissionand a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage. MethodsWe vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA). ResultsPCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not. ConclusionThis study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection.

Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance

BackgroundThe cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. MethodsWe performed a systematic review of randomized controlled trials and observational studies published between January 2010 – August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). ResultsOf 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and −14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. ConclusionsIn contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

Humoral and Cellular Immune Responses Induced by Bivalent DNA Vaccines Expressing Fusion Capsid Proteins of Porcine Circovirus Genotypes 2a and 2b.

Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated disease (PCVAD) that profoundly impacts the swine industry worldwide. While most of the commercial PCV vaccines are developed based on PCV genotype 2a (PCV2a), PCV genotype 2b (PCV2b) has become predominant since 2003. In this study, we developed and evaluated DNA-based bivalent vaccines covering both PCV2a and PCV2b. We generated a new immunogen, PCV2b-2a, by combining consensus sequences of the PCV2a and PCV2b capsid proteins (Cap2a and Cap2b) in a form of fusion protein. We also examined whether modifications of the PCV2b-2a fusion protein with a signal sequence (SS) and granulocyte macrophage-colony stimulating factor (GM-CSF) fusing with interleukine-4 (IL-4) (GI) could further improve the vaccine immunogenicity. An immunogenicity study of BALB/cAJcl mice revealed that the DNA vector pVAX1 co-expressing PCV2b-2a and GI (pVAX1.PCV2b-2a-GI) was most potent at inducing both antibody and cellular immune responses against Cap2a and Cap2b. Interestingly, the vaccines skewed the immune response towards Th1 phenotype (IgG2a > IgG1). By performing ELISA and ELISpot with predicted epitope peptides, the three most immunogenic B cell epitopes and five putative T cell epitopes were identified on Cap2a and Cap2b. Importantly, our DNA vaccines elicited broad immune responses recognizing both genotype-specific and PCV2-conserved epitopes. Sera from mice immunized with the DNAs expressing PCV2b-2a and PCV2b-2a-GI significantly inhibited PCV2a cell entry at serum dilution 1:8. All these results suggest a great potential of our PCV2b-2a-based vaccines, which can be further developed for use in other vaccine platforms to achieve both vaccine efficacy and economical production cost.

Characteristics of &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; carriage in the pediatric population

Objective: to investigate the regional peculiarities of Streptococcus pneumoniae carriage in the pediatric population and characterize the dominant serotypes of the pathogen.&#x0D; Materials and methods. The clinical study group consisted of 509 healthy children attending preschool institutions. Examination of nasopharyngeal samples for the detection of S. pneumonae was carried out by classical bacteriological and molecular biological methods. The serotype was determined by real-time PCR. Genome-wide sequencing of the serogroups 15 and 11 isolates and bioinformatic analysis were performed.&#x0D; Results. The S. pneumoniae bacterial carriers in the group of healthy children was detected in 207 children (40.7%), while the frequency of detection of S. pneumoniae in urban children living in Kazan was significantly higher than in children living in rural area and amounted to 53.4 and 31.1%, respectively (p 0.05). Among children vaccinated with the 13-valent pneumococcal conjugate vaccine (PCV-13), S. pneumoniae carriers were not detected in 57.5% of cases. There were no significant differences in the degree of nasopharyngeal contamination depending on the vaccination status. Analysis of the serotype composition indicates the predominance of vaccine serotypes (57.7%), while the share of serotypes included in the PСV-13 vaccine accounts for only 24.7%, the share of non-vaccine serotypes was 32.1%, untyped — 10.2%. In unvaccinated children, vaccine serotypes that are part of the PCV-13 and 23-valent polysaccharide pneumococcal vaccine prevailed (PPSV-23): 6ABCD (21%), 11 AD (15%), 14 (13%). In vaccinated children, serotypes not included in the active vaccines dominated: 15AF (17.4%), 23A (19.2%), as well as 11AD (19.6%) (11А is included in PPSV-23). The 27 Kz isolate (serotype 15C) belonged to one of the most common sequence types ST1025. The 105_Kz isolate (serotype 11D) belonged to another common sequence type ST 62.&#x0D; Conclusion. In order to improve epidemiological surveillance of pneumococcal infection, it is necessary to introduce the monitoring of circulating clonal complexes of dominant S. pneumoniae serogroups and analyze the genetic determinants of antibiotic resistance and virulence depending on the sequence type.

Impact of Demographic Developments and PCV13 Vaccination on the Future Burden of Pneumococcal Diseases in Germany—An Integrated Probabilistic Differential Equation Approach

Streptococcus pneumonia is the primary cause of morbidity and mortality in infants and children globally. Invasive pneumococcal disease (IPD) incidence is affected by various risk factors such as age and comorbidities. Additionally, this bacterium is a major cause of community-acquired pneumonia (CAP), leading to higher rates of hospitalization, especially among older adults. Vaccination with pneumococcal conjugate vaccines (PCVs) has proven effective, but the demographic transition in Germany poses a challenge. This study introduces a novel stochastic approach by integrating a population forecast model into a transmission dynamic model to investigate the future burden of pneumococcal diseases in three age groups (0–4, 5–59, and 60 and older). Our simulations, presented through mean predictions and 75% prediction intervals, indicate that implementing PCV13 (13-valent pneumococcal conjugate vaccine) until the year 2050 results in reduced cases of IPD and CAP in all age groups compared to scenarios without infant vaccination. However, cases with non-vaccine serotypes may persist at higher levels compared to scenarios without infant vaccination. Consequently, there may be a need for improvement in the current national vaccine policy, such as implementing the use of higher-valent PCVs and strengthening adult vaccination uptake.

Enhancing Immune Response in Non-Small-Cell Lung Cancer Patients: Impact of the 13-Valent Pneumococcal Conjugate Vaccine.

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients' and physicians' awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life.