13-valent Pneumococcal Conjugate Vaccine Research Articles

Increase in prevalence of Streptococcus pneumoniae serogroup 24 in children upon introducing 13-valent pneumococcal conjugate vaccine in Japan.

After introducing the 13-valent pneumococcal conjugate vaccine (PCV13) for children, a change in the prevalence of different Streptococcus pneumoniae serotypes that cause invasive pneumococcal diseases (IPDs) has been observed. The prevalence of vaccine serotypes has decreased and that of non-vaccine serotypes has increased. Currently, serogroup 24 has become one of the major non-vaccine serotypes causing IPDs in children in Japan. The aim of this study was to characterize clinical and genomic features of S. pneumoniae serogroup 24 strains isolated from sterile body sites in Japanese children. Serotyping, multi-locus sequence typing and genomic analysis of capsular polysaccharides of 61 strains of serogroup 24 were performed from 2015 to 2021. Among the 61 strains, 36, 23 and two belonged to serotypes 24F, 24B and 24C, respectively. The 24F sequence type (ST) 2572 and 24B ST 2572 were the major serotypes and sequence types observed from 2015 to 2019. By contrast, 24F ST 162 and 24B ST 2754 were the two major serotypes and sequence types observed after 2020. Two strains of serotype 24C were detected for the first time in Japan. Sequence analysis of the abpA gene, which plays a role in the synthesis of capsular polysaccharides in S. pneumoniae , was performed to distinguish different strains of serogroup 24. After the introduction of PCV13 in Japan, serogroup 24 has become one of the most prevalent non-vaccine serotypes causing IPDs in children. This serogroup has not been targeted in the next-generation pneumococcal conjugate vaccines. Therefore, monitoring of S. pneumoniae serogroup 24 that causes IPDs in children is essential.

Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

BackgroundThis phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F. MethodsHealthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F. Results1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 μg/mL (lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose.Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates. ConclusionA two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F.

CASE REPORT OF A CHILD DIAGNOSED WITH FIVE SEROTYPES / SEROGROUPS OF S. PNEUMONIAE

Streptococcus pneumoniae is one of the most common causes of widespread diseases. Pneumococci colonize asymptomatically the nasopharynx in children and could be responsible for severe, life-threatening illnesses such as pneumonia, sepsis and meningitis. The case report shows co-colonisation in two-year-old child vaccinated with the 10-valent pneumococcal conjugate vaccine (PCV-10) suffering from recurring catarrh and found to carry 5 serotypes S. pneumoniae. The strains have been detected and typed using molecular methods: real-time polymerase chain reaction (real-time PCR) and allelic hybridization. Monitoring S. pneumoniae colonization of human mucosa is crucial to reduce the likelihood of severe invasive pneumococcal diseases such as meningitis, pneumonia or otitis.

Genomic Epidemiology of Streptococcus pneumoniae Isolated in a Tertiary Hospital in Beijing, China, from 2018 to 2022.

Streptococcus pneumoniae is one of the most common bacterial pathogens of a wide range of community-acquired infections. It has been more and more recognized that this bacterium could also play a role as a cause of nosocomial infections. In this study, by retrospective analysis of the phenotypic resistance characteristics and genomic characteristics of 52 S. pneumoniae isolates in a hospital in Beijing, China, from 2018 to 2022, we explored the carriage of resistance genes and mutations in penicillin-binding proteins corresponding to the resistances, and identified the population diversity based on the prediction of serotypes and identification of sequence types (STs). The isolates displayed resistances to erythromycin (98%), tetracycline (96%), sulfonamide (72%) and penicillin G (42%). Among the 52 isolates, 41 displayed multiple-drug resistance. In total, 37 STs and 21 serotypes were identified, and the clonal complex 271 serogroup 19 was the most prevalent subtype. Only 24 isolates (46.2%) of 7 serotypes were covered by the 13-valent pneumococcal conjugate vaccination. The isolates showed high carriages of resistance genes, including tet(M) (100%) and erm(B) (98.1%); additionally, 32 isolates (61.5%) had mutations in penicillin-binding proteins. We also observed 11 healthcare-associated infections and 3 cases infected by different subtypes of isolates. We did not find nosocomial transmissions between the patients, and these cases might be associated with the asymptomatic colonization of S. pneumoniae in the human population. Our results called for further active surveillance of these subtypes, as well as the continuous optimization of the treatment protocols.

Antibiotic resistance pattern, capsular types, and molecular characterization of invasive isolates of Streptococcus pneumoniae in the south of Tunisia from 2012 to 2018

BackgroundStreptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide. In this study, we sought to analyze serotype distributions, antibiotic resistance, and genetic relationships of 106 clinical invasive pneumococcal isolates recovered in Tunisia between 2012 and 2018, prior to the routine use of pneumococcal conjugate vaccines (PCV).MethodsWe used multiplex PCR, the disk diffusion method and/or E-test, and multi-locus sequence typing (MLST).ResultsThe most frequent serotypes were 14 (17%), 19F (14.2%), and 3 (11.3%). Of the 106 S. pneumoniae isolates, 67.9% were penicillin non-susceptible (29.4% were resistant), 45.3% were amoxicillin non-susceptible (17% were resistant), and 16% were cefotaxime non-susceptible. For antibiotics other than β-lactams, resistance rates to erythromycin, tetracycline, cotrimoxazole, and chloramphenicol were 62.3, 33, 22.6, and 4.7%, respectively. Two isolates were non-susceptible to levofloxacin. Among 66 erythromycin-resistant pneumococci, 77.3% exhibited the cMLSB phenotype, and 87.9% carried ermB gene. All tetracycline-resistant strains harbored the tetM gene. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccines were 55.7, 57.5, and 81.1%, respectively. A multilocus sequence typing analysis revealed great diversity. Fifty different sequence types (STs) were identified. These STs were assigned to 10 clonal complexes and 32 singletons. The most common STs were 179, 2918, 386, and 3772 – related mainly to 19F, 14, 6B/C, and 19A serotypes, respectively.ConclusionsThis study demonstrated that the majority of the serotypes of invasive pneumococci in the Tunisian population were 14, 19F, and 3. Moreover, we noted a high degree of genetic diversity among invasive S. pneumoniae isolates. The highest proportions of antibiotic non-susceptible isolates were for penicillin, erythromycin, and tetracycline. Further molecular characteristics are required to monitor the genetic variations and to follow the emergence of resistant pneumococci for the post-vaccination era in Tunisia.

The safety of pneumococcal vaccines at the time of sequential schedule: data from surveillance of adverse events following 13-valent conjugated pneumococcal and 23-valent polysaccharidic pneumococcal vaccines in newborns and the elderly, in Puglia (Italy), 2013-2020.

Nowadays, two types of anti-pneumococcal vaccine are available: pneumococcal 13-valent conjugate vaccine (PCV13), first licensed in the United States (US) in 2013, and pneumococcal 23-valent polysaccaridic vaccine (PPSV23), first licensed in the US in 1999. These vaccines are recommended in Italy for the immunization of newborns and of the elderly, using a combined sequential schedule for the latter. This report aims to describe the PCV13- and PPSV23-related AEFIs notified in Puglia in 2013-2020, in order to design these products' safety profile in a real-life scenario, three years after the official recommendation about the sequential schedule for people over 60 years of age. This is a retrospective observational study. Data were gathered from the list of AEFIs notified following PCV13 and PPSV23 administration in Puglia in 2013-2020. The number of administered vaccine doses was obtained from the regional immunization database. AEFIs were classified according to WHO's algorithm, and causality assessment was carried out in case of serious AEFIs. From January 2013 to December 2020, 764,183 doses of PCV13 and 40,382 doses of PPSV23 were administered in Puglia. In the same period, 71 PCV13 AEFIs (Reporting Rate: 9.29 x100,000 doses) and 5 PPSV23 AEFIs (Reporting Rate: 12.4 x100,000 doses) were reported. The overall male/female ratio in AEFIs was 0.85. The majority of AEFIs occurred in subjects aged less than 2 (64/76, 84.2%), while 10 out of 76 (13.2%) occurred in patients aged 60 or older. 22 AEFIs were classified as serious and for 12 (54.5%) causality assessment showed a consistent relationship with immunization. The most commonly reported symptoms were fever (Reporting Rate: 4.72 x100,000 doses) and neurological symptoms (Reporting Rate: 3.23 x100,000 doses). Only one death was notified, classified as non-vaccine-related. The benefit of pneumococcal vaccination appears to be greater than the risk of AEFIs for both PCV13 and PPSV23. In fact, AEFIs occur in less than 0.1‰ of patients and the majority of AEFIs are mild and self-limiting.

Incidence of acute otitis media from 2003 to 2019 in children ≤ 17 years in England

BackgroundThe 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the UK. PCVs are active immunization for the prevention of invasive disease, pneumonia and acute otitis media (AOM) caused by Streptococcus pneumoniae in children.The aim of this observational study was to estimate incidence rates (IRs) of AOM in children ≤17 years from 2003 to 2019 in England, before and after the introduction of pneumococcal conjugate vaccines (PCVs).MethodsAOM episodes were identified using Read diagnosis codes in children aged ≤17 years in the Clinical Practice Research Datalink (CPRD) Gold database from 2003 to 2019. Annual IRs with 95% confidence intervals (CI) by age group were calculated as the number of episodes/person-years (PY) at risk. Interrupted time series analyses were conducted to estimate incidence rate ratios (IRR) across post-PCV7 (2007–2009), early post-PCV13 (2011–2014) and late post-PCV13 (2015–2019) periods compared to the pre-PCV7 period (2003–2005) using generalized linear models.ResultsFrom 2003 to 2019, 274,008 all-cause AOM episodes were identified in 1,500,686 children. The overall AOM IR was 3690.9 (95% CI 3677.1-3704.8) per 100,000 PY. AOM IRs were highest in children aged < 5 years and decreased by age; < 2 years: 8286.7 (95% CI 8216.8-8357.1); 2–4 years: 7951.8 (95% CI 7902.5-8001.4); 5–17 years: 2184.4 (95% CI 2172.1–2196.8) (per 100,000 PY). Overall AOM IRs declined by 40.3% between the pre-PCV7 period and the late-PCV13 period from 4451.9 (95% CI 4418.1-4485.9) to 2658.5 (95% CI 2628.6-2688.7) per 100,000 PY, and across all age groups. IRRs indicated a significant decrease in AOM IRs in all the post-vaccination periods, compared to the pre-PCV7 period: post-PCV7 0.87 (95% CI 0.85–0.89), early post-PCV13 0.88 (95% CI 0.86–0.91), and late post-PCV13 0.75 (95% CI 0.73–0.78).ConclusionsThe AOM IRs declined during the 2003–2019 period; however, the clinical burden of AOM remains substantial among children ≤17 years in England.

Combined 13-valent pneumococcal conjugate and 23-valent pneumococcal polysaccharide vaccine regimens for adults with systemic lupus erythematosus: Does the sequence of pneumococcal vaccination affect immunogenicity responses? A single-center cohort study in Brazil.

A combination of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is currently recommended for adults with systemic lupus erythematosus (SLE). However, data on the immunogenicity elicited by sequential pneumococcal vaccination in this patient population are scarce. In this study, we compared short-term antibody responses to both PCV13/PPSV23 (≥8-week interval) and PPSV23/PCV13 (≥12-month interval) vaccination strategies in pneumococcal vaccine-naive adults with SLE. This longitudinal, open-label, quasi-randomized study was performed in a single-center cohort of adults (18 years or older) with SLE. In both vaccination groups, blood samples were collected immediately before administering the first dose of the pneumococcal vaccine (timepoint T0), 4-6 weeks after the priming dose (T1), and 4-6weeks after the booster dose (T2). We focused on the 12 shared serotypes between PCV13 and PPSV23, and compared the following immunogenicity outcomes between the groups at T2: anti-pneumococcal antibody geometric mean concentration (ApAb GMC), fold increase in ApAb levels (FI-ApAb), overall seroprotection rate, and overall seroconversion rate. The protective level for each pneumococcal serotype was set at 1.3 μg/mL. We used the multi-analyte immunodetection method to determine serum levels of ApAbs. Thirty-four patients with SLE were screened between April 2019 and January 2020, and 16 of them (mean age: 39.4 years, 87.5% female, and 100% on immunosuppressants) had evaluable immunogenicity results at T2. The median time elapsed between the pneumococcal vaccinations was 56 days in the PCV13/PPSV23 group (n = 11 patients) and 16 months in the PPSV23/PCV13 group (n = 5 patients). Priming with PCV13 (PCV13/PPSV23 group), as opposed to PPSV23 (PPSV23/PCV13 group), yielded significantly better results regarding FI-ApAb, overall seroconversion rate, and overall seroprotection rate 4-6 weeks after each pneumococcal vaccination. A trend toward augmented ApAb GMC in the patients who received the PCV13/PPSV23 sequence was also observed. No relevant safety issues were identified with sequential pneumococcal vaccination. The PCV13-priming PPSV23-boost strategy in adults with SLE induced greater antibody responses for most immunogenicity outcomes than those elicited by the PPSV23/PCV13 strategy.

Single-centre, cross-sectional study on the factors and reasons for non-vaccination among patients with rheumatoid arthritis.

We aimed to investigate the vaccination coverage and the factors associated with non-vaccination for vaccine-preventable diseases among patients with rheumatoid arthritis. This single-centre, cross-sectional study was conducted in a 715-bed regional tertiary-care teaching hospital in Japan from 1 September to 30 November 2020. Vaccination status and the factors and reasons for not receiving the influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), and varicella vaccine live (VVL) were investigated. Among 991 patients, the vaccination coverage for the influenza vaccine, PPSV23, PCV13, and VVL was 62%, 46%, 14%, and 3%, respectively. The most common reasons for vaccine hesitancy were efficacy concerns for the influenza vaccine, safety concerns for the PPSV23 and PCV13, and both efficacy and safety concerns for the VVL. Younger age, no use of biologics or other hospital visits, and public assistance were factors significantly associated with non-vaccination for the influenza vaccine; younger age, short disease duration, and no visits to other hospitals for PPSV23; younger age, no hospitalisation, more experienced doctor, and no medical immunodeficiency for PCV13. We found that the factors associated with non-vaccination varied by vaccine type; therefore, vaccinations should be promoted with individualised strategies.

P06 The 15-valent pneumococcal conjugate vaccine (PCV) V114 induces cross-reactive antibodies against pneumococcal serotype 6C

Abstract Background Pneumococcal serotype 6C has structural similarity with serotype 6A and, to a lesser degree, serotype 6B. The 13-valent PCV (PCV13), which contains serotypes 6A and 6B, induces cross-reactive opsonophagocytic killing activity (OPA) antibodies to serotype 6C, with an observed decline in 6C disease incidence. V114 is a 15-valent PCV containing the 13 serotypes in PCV13 and two unique serotypes (22F and 33F). This study evaluated whether V114 elicits cross-reactive OPA antibodies to serotype 6C. Methods OPA antibodies to serotypes 6A, 6B, and 6C were evaluated in serum samples taken pre-vaccination and 30 days post-vaccination (single dose) from adults ≥50 years of age, and 30 days pre- and post-dose 4 from toddlers 12–15 months of age at fourth dose, who received V114 or PCV13 in the adult and paediatric V114 phase II proof-of-concept studies, respectively. The degree of inhibition of OPA antibody activity for serotypes 6A, 6B, and 6C after adsorption with serogroup 6 polysaccharides was evaluated in adult samples. Results Samples from 250 adults (V114, n=150; PCV13, n=100) and 150 paediatric participants (V114, n=100; PCV13, n=50) were included. In both the adult and paediatric populations, observed OPA geometric mean titres (GMTs) to serotypes 6A, 6B, and 6C were comparable across vaccination groups; however, the cross-reactive response to serotype 6C was stronger in infants than adults. The inhibition analysis demonstrated the specificity of antibody responses. Conclusions V114 induces cross-reactive antibodies to serotype 6C in adult and paediatric populations that are specific and comparable to those induced by PCV13.

P05 Safety, tolerability, and immunogenicity of V114 compared with PCV13 in preterm infants: a pooled subgroup analysis of four Phase III studies

Abstract Background Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants, mainly due to underlying comorbidities and immunological immaturity. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in 13-valent PCV (PCV13) plus two additional serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (&amp;lt;37 weeks gestational age) enrolled in 4 paediatric Phase III studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. Methods Safety was evaluated as the proportion of participants with AEs following each vaccination. Serotype-specific anti-pneumococcal IgG GMCs, IgG response rates, and OPA GMTs were measured at 30 days post-primary series (PPS; post-dose 3 [PD3]), pre-toddler dose, and 30 days post-toddler dose (PTD; post-dose 4 [PD4]). Results 174 and 180 participants received V114 and PCV13, respectively. Mean gestational age was 35.4 weeks (range: 27–37 weeks). Proportions of participants with any AE were comparable between vaccination groups following each vaccination; most solicited AEs were transient (≤3 days) and of mild-to-moderate intensity. V114-elicited IgG GMCs (Figure 1), IgG response rates, and OPA GMTs were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days PPS (PD3) and PTD (PD4). Conclusions In preterm infants, vaccination with V114 has an acceptable safety profile, is well tolerated, and induces comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to V114 serotypes 22F and 33F. Study results support use of V114 in preterm infants.

P07 A Phase 3 randomized, double-blind, comparator-controlled study to evaluate safety, tolerability and immunogenicity of V114 pneumococcal vaccine in haematopoietic cell transplant recipients (PNEU-STEM)

Abstract Background Allogeneic haematopoietic cell transplant (allo-HCT) represents a definitive therapy for a variety of haematological diseases. Immunosuppressive therapy following allo-HCT and graft-versus-host disease (GVHD) render the patient susceptible to infectious complications, including invasive pneumococcal disease. Post-allo-HCT pneumococcal vaccination is recommended 3–6 months after transplant in a multi-dose series to help prevent pneumococcal disease. Objectives V114 is a 15-valent pneumococcal conjugate vaccine (PCV) approved in adults, containing all 13 serotypes in Prevnar 13™ (PCV13; contains serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) as well as epidemiologically important serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 when given to allo-HCT recipients. Methods Individuals ≥3 years of age were randomized 1:1 to receive 3 doses of V114 or PCV13 in one-month intervals starting 3–6 months after allo-HCT. At 12 months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV if they experienced chronic GVHD. All participants or their legal representatives provided informed consent at enrolment. Primary safety objective was to evaluate the proportion of participants with adverse events (AEs) within each vaccination group for 3 to &amp;lt;18 years old and ≥18 years old age groups. Primary immunogenicity objective was to evaluate serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) for all 15 V114 serotypes at 30 days following the third PCV dose (Day 90) in each vaccination group. A key secondary objective was to evaluate opsonophagocytic activity (OPA) geometric mean titres (GMTs) for all V114 serotypes at Day 90. Results A total of 274 subjects (14 children [3 to &amp;lt;18 years of age] and 260 adults ≥18 years old) were enrolled and vaccinated in the study. The proportion of participants with systemic AEs and serious AEs after any dose of study vaccine were generally comparable between intervention groups in the paediatric and adult cohorts. V114 recipients reported a higher proportion of injection-site AEs and vaccine-related systemic AEs compared with PCV13 in the adult cohort. Of all vaccinated participants, 32.4% experienced serious AEs during the study (28.8% in V114 group, 36.3% in PCV13 group). Seventeen participants (5.8% in V114 group, 6.7% in PCV13 group) died during the study. None of the deaths was determined by the investigator to be related to study vaccines. For both IgG GMCs (Table 1) and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. Conclusions V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13 for both paediatric and adult participants. Despite the immunocompromised status of the participants, the study vaccines induced serotype-specific immunogenicity and V114 induced generally comparable responses to PCV13 by IgG GMCs and OPA for the 13 shared serotypes at Day 90. In addition, V114 induced higher antibody responses than PCV13 for serotypes unique to V114 (22F and 33F). Study results support the use of V114 in allo-HCT recipients.

Frequent Transmission of Streptococcus pneumoniae Serotype 35B and 35D, Clonal Complex 558 Lineage, across Continents and the Formation of Multiple Clades in Japan.

Streptococcus pneumoniae is a common bacterial pathogen that causes infections in children worldwide, even after administration of the pneumococcal conjugate vaccine. S. pneumoniae serotype 35B, especially the clonal complex 558 (CC558) lineage, has emerged globally following implementation of the 13-valent pneumococcal conjugate vaccine. Serotype 35B strains are also associated with multidrug resistance to both β-lactams and non-β-lactam drugs. In addition, a novel serotype, 35D, which is closely related to 35B and differs in polysaccharide structure, was recently reported. However, the genetic relationship among globally disseminating serotype 35B and D (35B/D) strains remains unknown. To investigate the molecular epidemiology of global serotype 35B/D strains, we conducted a genomic analysis of serotype 35B/D strains from various continents, including those from the Japanese national surveillance collection. A total of 87 isolates were identified as serotype 35B/D in the Japanese surveillance collection (n = 1,358). All the isolates were assigned to either CC558 or CC2755. Serotype 35D isolates were interspersed with serotype 35B isolates. Phylogenetic analysis revealed the formation of multiple clusters by the Japanese serotype 35B/D-CC558 isolates among the foreign isolates, which suggested multiple events of introduction of the clone into Japan. The global 35B/D-CC558 strains were found to share specific penicillin-binding protein profiles, pbp1a-4, pbp2b-7, and pbp2x-7, associated with penicillin, cephalosporin, and carbapenem nonsusceptibility. Moreover, 88.5% of the Japanese 35B/D-CC558 and 35B/D-CC2755 isolates were found to harbor the Tn916-like integrative and conjugative elements Tn2009, Tn2010, and Tn6002, associated with multidrug resistance to macrolides and tetracyclines. The results of this study imply that serotype 35B/D-CC558 strains could be frequently transmitted intercontinentally.

Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial

Three pneumococcal conjugate vaccines (PCVs) are currently licensed and WHO prequalified for supply by UN agencies. Here, we aimed to investigate the safety and immunogenicity of SIIPL-PCV compared with PHiD-CV and PCV13, when administered to infants according to a 2 + 1 schedule. This single-centre, double-blind, active-controlled, randomised, phase 3 trial was done in Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine clinical trial facilities within two government health centres in the western region of The Gambia. Healthy, PCV-naive infants aged 6-8 weeks were enrolled if they weighed at least 3·5 kg and had no clinically significant health complaints, as determined by history and clinical examination. Eligible infants were randomly assigned (1:1:1) to receive either SIIPL-PCV, PHiD-CV, or PCV13 using permuted blocks of variable size. Parents and the trial staff assessing all study outcomes were masked to vaccine group. The first PCV vaccine was given with other routine Expanded Programme on Immunization vaccines when infants were aged 6-8 weeks (visit 1). At visit 2, routine vaccines alone (without a PCV) were administered. At visit 3, the second dose of the PCV was administered alongside other routine vaccines. At visit 4, a blood sample was collected. Visits 1-4 took place at intervals of 4 weeks. The booster PCV was administered at age 9-18 months (visit 5), with final follow-up 4 weeks after the booster (visit 6). The primary immunogenicity outcome compared the serotype-specific IgG geometric mean concentrations (GMCs) generated by SIIPL-PCV with those generated by PHiD-CV and PCV13, 4 weeks after the booster. We used descriptive 95% CIs without adjustment for multiplicity. Immunogenicity analyses were done in the per protocol population (defined as all children who received all the assigned study vaccines, who had an immunogenicity measurement available, and who had no protocol deviations that might interfere with the immunogenicity assessment). This trial was registered with the Pan African Clinical Trials Registry, PACTR201907754270299, and ClinicalTrials.gov, NCT03896477. Between July 18 and Nov 14, 2019, 745 infants were assessed for study eligibility. Of these, 85 infants (11%) were ineligible and 660 (89%) were enrolled and randomly assigned to receive SIIPL-PCV (n=220), PHiD-CV (n=220), or PCV13 (n=220). 602 infants (91%) were included in the per protocol immunogenicity population. The median age at vaccination was 46 days (range 42-56). 342 infants (52%) were female and 318 (48%) were male. Post-booster serotype-specific IgG GMCs generated by SIIPL-PCV ranged from 1·54 μg/mL (95% CI 1·38-1·73) for serotype 5 to 12·46 μg/mL (11·07-14·01) for serotype 6B. Post-booster GMCs against shared serotypes generated by PHiD-CV ranged from 0·80 μg/mL (0·72-0·88) for serotype 5 to 17·31 μg/mL (14·83-20·20) for serotype 19F. Post-booster GMCs generated by PCV13 ranged from 2·04 μg/mL (1·86-2·24) for serotype 5 to 15·54 μg/mL (13·71-17·60) for serotype 6B. Post-booster IgG GMCs generated by SIIPL-PCV were higher than those generated by PHiD-CV for seven of the eight shared serotypes (1, 5, 6B, 7F, 9V, 14, and 23F). The GMC generated by serotype 19F was higher after PHiD-CV. The SIIPL-PCV to PHiD-CV GMC ratios for shared serotypes ranged from 0·64 (95% CI 0·52-0·79) for serotype 19F to 2·91 (2·47-3·44) for serotype 1. The serotype 1 GMC generated by SIIPL-PCV was higher than that generated by PCV13, whereas serotype 5, 6A, 19A, and 19F GMCs were higher after PCV13. The SIIPL-PCV to PCV13 GMC ratios ranged from 0·72 (0·60-0·87) for serotype 19A to 1·44 (1·23-1·69) for serotype 1. SIIPL-PCV was safe and immunogenic when given to infants in The Gambia according to a 2 + 1 schedule. This PCV is expected to provide similar protection against invasive and mucosal pneumococcal disease to the protection provided by PCV13 and PHiD-CV, for which effectiveness data are available. Generating post-implementation data on the impact of SIIPL-PCV on pneumococcal disease endpoints remains important. Bill & Melinda Gates Foundation.

Cost-Effectiveness Analysis of Routine Use of 15-Valent Pneumococcal Conjugate Vaccine in the US Pediatric Population.

This study evaluated the clinical and economic impact of routine pediatric vaccination with the 15-valent pneumococcal conjugate vaccine (PCV15, V114) compared with the 13-valent PCV (PCV13) from a societal perspective in the United States (US). A Markov decision-analytic model was constructed to estimate the outcomes for the entire US population over a 100-year time horizon. The model estimated the impact of V114 versus PCV13 on pneumococcal disease (PD) incidence, post meningitis sequalae, and deaths, taking herd immunity effects into account. V114 effectiveness was extrapolated from the observed PCV13 data and PCV7 clinical trials. Costs (2021$) included vaccine acquisition and administration costs, direct medical costs for PD treatment, direct non-medical costs, and indirect costs, and were discounted at 3% per year. In the base case, V114 prevented 185,711 additional invasive pneumococcal disease, 987,727 all-cause pneumonia, and 11.2 million pneumococcal acute otitis media cases, compared with PCV13. This led to expected gains of 90,026 life years and 96,056 quality-adjusted life years with a total saving of $10.8 billion. Sensitivity analysis showed consistent results over plausible values of key model inputs and assumptions. The findings suggest that V114 is a cost-saving option compared to PCV13 in the routine pediatric vaccination program.

Epidemiología molecular de la colonización nasofaríngea neumocócica en niños de Sevilla, tras la implementación del programa de vacunación con VNC13 en Andalucía (España)

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination program was introduced in December 2016 in Andalusia. MethodsA cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period) were used for comparison of serotype/genotype distributions and antibiotic resistance rates. ResultsOverall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11 vs. 38%, P=0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (P=0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. ConclusionsThere was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

ABSTRACT This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Phase 3 trial to evaluate the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by 23-valent pneumococcal polysaccharide vaccine 6 months later, in at-risk adults 18–49 years of age (PNEU-DAY): A subgroup analysis by baseline risk factors

ABSTRACT Immunocompetent adults with certain medical and behavioral factors are at increased risk of pneumococcal disease. In some countries, sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults. This subgroup analysis from a phase 3 study evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults 18–49 years of age with pre-defined risk factors for pneumococcal disease. Safety and immunogenicity post-vaccination were analyzed by type and baseline number of risk factors for pneumococcal disease (1 and ≥2 risk factors). This analysis included 1,131 participants randomized 3:1 to receive either V114 or PCV13, followed by PPSV23. The majority (73.1%) of participants had at least one risk factor. Safety and tolerability profiles of V114 and PCV13 were similar across risk factor groups. V114 administered either alone or sequentially with PPSV23 6 months later was immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of the number of baseline risk factors. V114 has the potential to broaden serotype coverage for at-risk adults.

Противопневмококковая иммунизация у детей раннего возраста с хронической сердечной недостаточностью

Aim: To determine the coverage, efficacy and tolerability of pneumococcal vaccination in young children with cardiovascular disease associated with chronic heart failure. Design: Retro- and prospective randomized comparative study. Materials and methods. The study included 250 patients at the age of 2 months to 5 years with confirmed chronic cardiac failure caused by cardiomyopathy or congenital heart disorder. Within the scope of a specialised laboratory and instrumental examination, all children underwent an assessment of specific immunoglobulin (Ig) levels to the most common pneumococcal serotypes (1-5, 6B, 7F, 8, 9N, 9V, 10A, 11A,12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) using VaccZyme Anti-PCP IgG test system. During consultations and vaccination schedule development, pneumococcal vaccination coverage and the reasons for long-term medical exemptions or refusals were analysed. Provided the primary disease was stable, there were no contraindications and a parent gave their consent, patients were vaccinated with 13-valent pneumococcal conjugate vaccine (PCV13). Results. When questioning the parents of patients, it was revealed that before admission to the department, only 97 (38.8%) patients received at least 1 dose of pneumococcal vaccine, while the remaining 153 (61.2%) were not vaccinated. During hospitalization, 65 (42.5%) of 153 unvaccinated patients under 5 years of age who had not received a single pneumococcal vaccine received the first dose (V1) of PCV13; of 97 children vaccinated, 20 (20.6%) received a second dose, 18 (18.6%) — pneumococcal booster. There was a significant difference in the levels of antibodies to Streptococcus pneumoniae between the group of patients who received a full course of immunization according to age and the group of unvaccinated children: 108.1 ± 58.4 vs. 12.14 ± 7.8 mg/l (p &lt; 0.05). In children with an incomplete course of vaccination, the levels of specific IgG to pneumococcal serotypes were lower. In groups of children who received only one dose of the vaccine in the first or second year of life, they amounted to 42.2 ± 11.7 and 40.2 ± 16.2 mg/l, respectively. Children who received at least two doses of vaccine without revaccination (starting before 12 months) had a relatively higher level of 68.2 ± 6.3 mg/L. But, despite a clear trend, there was no significant difference between these groups in our study. In the post-vaccination period, no serious complications were recorded in the examined children. Conclusion. Vaccination against pneumococcal infection in children with chronic heart failure is effective, safe and should be carried out as close as possible to the schedule of the national vaccination calendar, with a limited set of contraindications. Keywords: vaccination, 13-valent pneumococcal conjugate vaccine, immunoglobulin G, chronic heart failure.

A phase 3, randomized, controlled, open-label study to evaluate the persistence up to 5 years of 1 or 2 doses of meningococcal conjugate vaccine MenACWY-TT given with or without 13-valent pneumococcal conjugate vaccine in 12–14-month-old children

BackgroundImmunogenicity and safety up to 5 years after administration of 1 or 2 doses of quadrivalent meningococcal serogroup A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) given alone or with 13-valent pneumococcal conjugate vaccine (PCV13) in children was investigated. MethodsThis phase 3 study randomized healthy 12–24-month-olds to MenACWY-TT at Month 0 (ACWY1d), MenACWY-TT at Months 0 and 2 (ACWY2d), MenACWY-TT and PCV13 at Month 0 (Co-Ad), or PCV13 at Month 0 and MenACWY-TT at Month 2 (PCV13/ACWY). Immune responses 1, 3, and 5 years after primary vaccination were evaluated with serum bactericidal activity using rabbit complement (rSBA) titers ≥ 1:8 and geometric mean titers (GMTs). Evaluation of serious adverse events up to 5 years after primary vaccination are reported. ResultsOf the 802 children randomized in the study, 619 completed the study through Year 5. Immune responses after vaccination declined over time but were higher 5 years after vaccination compared with levels before vaccination. At Year 5, the percentages of children with rSBA titers ≥ 1:8 across all serogroups were 20.5 %−58.6 %, 28.4 %−65.8 %, 23.9 %−52.8 %, and 19.4 %−55.8 % in the ACWY1d, ACWY2d, Co-Ad, and PCV13/ACWY groups, respectively. Comparable antibody persistence at Year 5 was observed for participants receiving 1 or 2 doses of MenACWY-TT, although GMTs were elevated in those who received 2 versus 1 dose. The percentage of children with protective antibody titers at Year 5 was similar in participants who received PCV13 and MenACWY-TT compared with that observed for participants who only received 1 or 2 MenACWY-TT doses. No new safety concerns were identified during the study period. ConclusionAntibody responses persisted in the majority of children up to 5 years after primary vaccination with MenACWY-TT administered in a 1- or 2-dose regimen with or without PCV13, with no new safety concerns identified.ClinicalTrials.gov Identifier NCT01939158; EudraCT number 2013–001083-28.