13-valent Pneumococcal Conjugate Vaccine Research Articles

Nasopharyngeal carriage of Streptococcus pneumoniae among children and their household members in southern Mozambique five years after PCV10 introduction.

Streptococcus pneumoniae is an important cause of pneumonia, sepsis, and meningitis, which are leading causes of child mortality. Pneumococcal conjugate vaccines (PCVs) protect against disease and nasopharyngeal colonization with vaccine serotypes, reducing transmission to and among unvaccinated individuals. Mozambique introduced 10-valent PCV (PCV10) in 2013. In 2017-2019, 13-valent PCV (PCV13) replaced PCV10, and in September 2019 the schedule changed from three primary doses to two primary doses and a booster; the booster-containing schedule may increase indirect effects. We examined pneumococcal carriage in Mozambique to establish a baseline for estimating the impact of policy changes and to estimate the long-term impact of PCV10 in children aged <5years. We calculated prevalence of carriage of PCV10 serotypes and the 3 additional PCV13 serotypes ('PCV13-unique') among children aged <5years and their household members in southern Mozambique, between October 2018 and July 2019. Nasopharyngeal swabs were cultured, and isolates underwent Quellung serotyping. For children, we compared these "long-term post-PCV10" data with prior surveys ("pre-PCV" (2012-2013) and "post-PCV10" (2015-2016)) that used the same methods. In 2018-2019, among 1319 children aged under five years, 1064 (80.7%) were colonized with pneumococcus, among 614 children aged 5-<18years, 355 (57.8%) were colonized, and among 804 adults (aged ≥18years), 285 (35.4%) were colonized. The most frequently observed serotypes were 19A (n=154, 8.5% of isolates) and 6A (n=107, 5.9%), both PCV13-unique serotypes. Overall carriage prevalence among children under five years remained stable at approximately 80% across the carriage studies conducted between 2012 and 2019; between 2015 and 2016 and 2018-2019, the prevalence of PCV10-type carriage declined from 17.7% to 10.1%. Despite substantial declines in PCV10-type carriage initially following vaccine introduction, the continued circulation of PCV10 serotypes and relative high prevalence of PCV13-unique serotypes underscore the need to understand the impact of policy changes on pneumococcus transmission.

Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial.

Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9months (1+1 co-administration) or YF vaccine administered separately at age 10months (1+1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9months (3+0 separate). Blood samples were collected 28-35days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres≥1:8 were calculated with 95% confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than-10%. Forty-eight, 66, and 98 participants enrolled in 3+0 separate, 1+1 co-administration, and 1+1 separate groups respectively had NA results. Per protocol analysis of the 3+0 separate, 1+1 co-administration, 1+1 separate, and the combined 1+1 separate and 3+0 separate groups found that 81%, 85%, 92%, and 88% of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1+1 co-administration and 1+1 separate groups was -7% (95% CI, -18% to 3%). The difference between 1+1 co-administration and 3+0 separate groups was 4% (95% CI, -10% to 15%). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613.

Serotype-specific serum immunoglobulin G at 18 months of age following one or two doses of a primary series of 10-valent or 13-valent pneumococcal conjugate vaccine and a booster dose at nine months of age: a randomized controlled study

ABSTRACT Background Due to high costs of pneumococcal conjugate vaccines (PCV), transitioning from a two (2 + 1) to a single dose (1 + 1) primary series with a booster should be considered. This study evaluated the immune response at 18 months of age following a 1 + 1 compared to a 2 + 1 schedule of 10-valent (PCV10) and 13-valent (PCV13) vaccines. Research design and methods A single-center, open-label, randomized trial conducted in Soweto, South Africa, evaluated the immunogenicity of differing dosing schedule for PCV10 and PCV13. Six hundred children were randomly assigned to six study arms (1:1:1:1:1:1). Non-inferiority was concluded when the lower limit of the 96% confidence interval of the ratio of geometric mean concentrations (GMCs) of the 1 + 1 and 2 + 1 schedules was >0.5 for at least 10 and eight of the PCV13 and PCV10 serotypes, respectively. Results GMCs in children who received the PCV13_6w + 1 and PCV13_14w + 1 schedule were non-inferior for 11 and 10 of the PCV13 serotypes, respectively, compared with the PCV13_2 + 1 arm. For PCV10, GMCs for both 1 + 1 schedules were non-inferior to a 2 + 1 schedule for nine of the PCV10 serotypes. Conclusion Transitioning to a 1 + 1 schedule should be considered for early immunization programs. Clinical trial registration www.clinicaltrials.gov identifier is NCT02943902.

Characteristics of Invasive Pneumococcal Diseases Cases Among U.S. Children With Hematologic Malignancies Before and After Introduction of Thirteen-valent Pneumococcal Conjugate Vaccine, 2005-2019.

Children with hematologic malignancies (HMs) are at increased risk of invasive pneumococcal disease (IPD). Data on long-term IPD trends in U.S. children with HM after 13-valent pneumococcal conjugate vaccine (PCV13) introduction are limited. We assessed IPD trends in children with HM before and after PCV13 introduction and the proportion of IPD cases caused by serotypes contained in new pneumococcal conjugate vaccines (PCV15 and PCV20, introduced after 2019). During 2005-2019, IPD cases among children aged <18 years were identified through the Active Bacterial Core surveillance. We characterized IPD cases by underlying conditions (HM, other IPD risk factors, no IPD risk factors) and time periods [pre-PCV13 (2005-2009), early-PCV13 (2010-2014) and late-PCV13 (2015-2019)]. We estimated incidence rate ratios (IRRs) in children aged <5 years with and without HM and during 2010-2019. We identified 5912 cases of IPD in children aged <18 years; 215 (3.6%) were among children with HM. The proportion of IPD cases with PCV13 serotypes decreased over time in all risk groups; however, IRRs among children with vs. without HM were 215.8 [95% confidence interval (CI): 146.1-292.4] and 240.9 (95 CI: 152.3-341.1) in early and late-PCV13 periods, respectively. In late-PCV13 period, PCV15/non-PCV13 serotypes and PCV20/non-PCV15 serotypes caused 19.4% and 4.8% of IPD cases among children with HM. The proportion of PCV13-type IPD decreased in all children after PCV13 introduction. However, children with HM remain at an increased risk of IPD. Continued monitoring of the impact of PCV15 and PCV20 use among children with HM is needed.

Expanded Recommendations for Use of Pneumococcal Conjugate Vaccines Among Adults Aged ≥50 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

Before October 2024, the Advisory Committee on Immunization Practices (ACIP) recommended use of a pneumococcal conjugate vaccine (PCV) for all adults aged ≥65 years, as well as for those aged 19-64 years with risk conditions for pneumococcal disease who have not received a PCV or whose vaccination history is unknown. Options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals) or 21-valent PCV (PCV21; CAPVAXIVE; Merck Sharp & Dohme) alone or 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme). There are additional recommendations for use of PCV20 or PCV21 for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on expanding the age-based PCV recommendation to include adults aged 50-64 years. On October 23, 2024, ACIP recommended a single dose of PCV for all PCV-naïve adults aged ≥50 years. Recommendations for PCVs among adults aged 19-49 years with risk conditions and PCV13-vaccinated adults have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides updated clinical guidance for use of PCV.

Effect of mass campaigns with full and fractional doses of pneumococcal conjugate vaccine (Pneumosil) on the reduction of nasopharyngeal pneumococcal carriage in Niger: a three-arm, open-label, cluster-randomised trial.

In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger. In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign. Independently sampled carriage surveys were done among 2268 households 6 months before and after vaccination, collecting nasopharyngeal swabs from healthy children for culture and serotyping; those with contraindication to nasopharyngeal swabbing were excluded. The primary outcome was nasopharyngeal carriage of vaccine-serotype pneumococcus. We tested whether vaccine-type carriage was reduced in full-dose versus control clusters; and whether fractional doses were non-inferior to full-doses (lower bound 95% CI more than -7·5%), using generalised estimating equations to analyse cluster summaries at baseline and follow-up, controlling for covariates to estimate risk differences and their 95% CIs. The study is registered with ClinicalTrials.gov (NCT05175014) and the Pan-African Clinical Trials Registry (PACTR20211257448484). Surveys were done between Dec 22, 2021, and March 18, 2022, and between Dec 12, 2022, and March 9, 2023. The vaccination campaign ran from June 15 to Aug 2, 2022. Participants' characteristics were consistent across surveys and groups. Pre-vaccination, vaccine-type carriage was 15·6% (149 of 955 participants) in the full-dose group, 17·9% (170 of 948) in the fractional-dose group, and 18·8% (60 of 320) in the control group. Post-vaccination, vaccine-type carriage was 4·6% (44 of 967) in the full-dose group, 8·0% (77 of 962) in the fractional-dose group, and 16·5% (53 of 321) in the control group. The primary analysis showed a risk difference of -16·2% (95% CI -28·6 to -3·0) between the full-dose group and control group (p=0·002 for superiority), and -3·8% (-6·1 to -1·6) between the full-dose group and fractional-dose group, meeting the non-inferiority criteria. No adverse events were judged to be related to vaccination. Multi-age cohort campaigns had a marked effect on vaccine-type carriage and fractional-dose campaigns met non-inferiority criteria. Such campaigns should be considered in low-coverage settings, including humanitarian emergencies, to accelerate population protection. EDCTP2 programme supported by the EU. For the French translation of the abstract see Supplementary Materials section.

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: the PSERENADE project.

Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. Analyses included 10,168 cases <5y from PCV13 sites and 2,849 from PCV10 sites, 3,711 and 1,549 for 5-17y and 29,187 and 5,653 for ≥18y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 4874% across products and PCV7 impact strata for children <5y, 3562% for 5-17y and 036% for ≥18y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5y: 96100%; 5-17y: 7785%; ≥18y: 7385%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

Pneumococcal vaccines for prevention of adult pneumonia.

Streptococcus pneumoniae, pneumococcus, is one of most important bacterial pathogens in adult community-acquired pneumonia. Although it can cause a variety of illness including invasive diseases (IPD), pneumonia has a greater impact than IPD from the perspective of health economics. 23 valent pneumococcal polysaccharide vaccine (PPSV23) and 13 valent pneumococcal conjugate vaccine (PCV13) have been recommended for people ≥65 years old until recently based on evidence in preventing IPD and pneumonia. Because the introduction and dissemination of PCVs for infants and its effects on herd immunity have led 'serotype replacement' in adult IPD and pneumococcal pneumonia since the 2000s, serotypes targeted by vaccines have sifted accordingly. With the availability of PCV21 this year, in addition to PCV15 and PCV20, vaccine prevention strategies for adult pneumococcal pneumonia need to be reconsidered. In this narrative review, we discuss current and future challenges regarding pneumococcal vaccines to prevent adult pneumococcal pneumonia.

Changes in population genetic structure of serotype 19A Streptococcus pneumoniae after universal childhood use of the 10-valent pneumococcal conjugate vaccine in Brazil.

The introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) for nationwide childhood immunization in 2010 led to a significant reduction in colonization and invasive pneumococcal disease (IPD) by vaccine serotypes in young. However, non-vaccine serotypes have emerged, and serotype 19A is now the leading cause of IPD in Brazil. We analyzed 32 serotype 19A isolates of Streptococcus pneumoniae recovered from children and adults who attended different health facilities in the state of Rio de Janeiro, Brazil, between 2010 and 2023. The capsular types of the isolates were determined by sequential multiplex PCR or by cpsB gene sequencing. All isolates were subjected to antimicrobial susceptibility testing and MLST. Of the 32 serotype 19A isolates, 29 (90.6%) isolates were recovered from children aged ≤5years and three (9.4%) isolates were recovered from adults. Nineteen (59.4%) isolates were associated with colonization, and 13 (40.6%) isolates were from diseases. All isolates were susceptible to chloramphenicol, levofloxacin, linezolid, rifampin, and vancomycin. The highest frequencies of non-susceptibility (intermediate + resistant) were observed for sulfamethoxazole-trimethoprim (n=30; 93.8%), penicillin (n=24; 75%), and erythromycin (n=23; 71.9%). Twenty-two (68.8%) isolates were multidrug resistant (MDR). MICs for penicillin among penicillin-non-susceptible pneumococci (PNSP) ranged from 0.12 to 8.0μg/mL. MICs for erythromycin ranged from 0.064 to >256μg/mL. MICs for ceftriaxone ranged from 0.023 to 4μg/mL. The most common genetic lineages were ST733 (n=7; 21.9%), mostly found before and in the early years of PCV10 introduction, and CC320 (n=25; 78.1%), mostly found in the late-PCV10 period. All 25 isolates within CC320 were PNSP and mostly (n=22; 88%) MDR. We observed a shift in antimicrobial susceptibility profiles and genetic lineages after long-term use of PCV, mostly PCV10, for routine childhood immunization, characterized by clonal expansion of the MDR lineage CC320.

Single priming and a booster dose of 10-valent and 13-valent pneumococcal conjugate vaccine (PCV) maintains suppression of vaccine serotype colonization in South African children at 3, 4, and 5 years of age: a single-centre, open-labelled, randomized trial

ABSTRACT Background Surveillance on nasopharyngeal Streptococcus pneumoniae carriage in older children would be informative in determining whether a single priming and booster dose of pneumococcal conjugate vaccine (PCV) provides durable protection against pneumococcal disease compared with traditional dosing schedules. Methods and objectives We report on the secondary study objective to evaluate overall, vaccine-serotype (VT), and non-vaccine serotype (NVT) S. pneumoniae colonization at 3, 4, and 5 years of age in children who were randomized to receive 10-valent or 13-valent PCV formulations at 6 (6w + 1) or 14 (14w + 1) weeks compared with a two-dose primary series (2 + 1), with all children receiving a booster dose at 9 months of age, using a multiplex nanofluidic qPCR assay. Results The prevalence of overall, VT, or NVT at 5 years of age between the 2 + 1 compared with the 6w + 1 or 14w + 1 groups for both PCV10 and PCV13 did not differ. Conclusion Although inconclusive, our findings suggest that a reduced 1 + 1 PCV dosing schedule is unlikely to increase breakthrough cases of VT pneumococcal disease in older children, which can inform decision-making on transitioning to a 1 + 1 schedule in South Africa. Clinical trial registration: The trial is registered at www.clinicaltrials.gov (identifier is NCT04275284).

Pneumococcal serotypes missing prespecified efficacy threshold in immunogenicity trials: real-world evidence from national immunization programs

ABSTRACT Objectives The 13-valent (PCV13) and 10-valent (PCV10) pneumococcal conjugate vaccines missed non-inferiority for certain 7-valent (PCV7) serotypes in immunogenicity trials. This study examines the population-level IPD case trends for these serotypes. Methods We identified six countries with national IPD surveillance data that introduced PCV13 (Canada, Germany, Israel, Italy, South Africa, and the United States) and three with PCV10 (Finland, Brazil, and the Netherlands). We extracted country-specific annual IPD case counts for PCV7 serotypes that missed non-inferiority and met non-inferiority (6B + 23F and PCV7 minus [6B + 23F] serotypes for PCV10 countries; 6B +9V + 23F, and PCV7 minus [6B +9V + 23F] serotypes for PCV13 countries) in clinical trials. Case count data for each country were plotted for observed serotype trends in different age groups (<5 and ≥5 years) for 8 years following PCV13/PCV10 introduction. Results For all ages and countries, IPD cases due to PCV7 serotypes that missed non-inferiority either decreased or remained suppressed following PCV13/PCV10 introduction. Similar trends were found for PCV7 serotypes that met non-inferiority in those <5 years. Paradoxically, cases increased in those ≥5 years in Canada, Italy, and the US, primarily driven by increases in serotypes 4 and 19F disease. Conclusions Despite missing non-inferiority of serotypes in immunogenicity trials, higher-valent PCVs effectively suppressed these serotypes across all ages. Non-inferiority criteria from immunogenicity trials may not fully predict real-world disease impact after PCV implementation.

Economic evaluation of childhood pneumococcal conjugate vaccination programs in Qinghai and Hainan provinces, China

ABSTRACT Background The burden of pneumococcal disease varies regionally in China, particularly affecting children in Qinghai and Hainan. Nevertheless, absence of pneumococcal conjugate vaccine (PCV) in the National Immunization Program (NIP) or local programs presents limited coverage. This study evaluated the health and economic impact of including PCV in immunization programs in Qinghai and Hainan. Research design and methods A decision tree Markov model was constructed to simulate health outcomes and lifetime costs among children under different 13-valent PCV (PCV13) vaccination strategies compared to current practices, from societal and healthcare perspectives. Data on epidemiology, vaccine efficacy, cost, and utility were obtained from literature or open databases. Sensitivity analyses were conducted to explore parameter uncertainty. Results Including three-dose PCV13 in provincial programs at NIP coverage (98.91%) could avert 7100 episodes and 118 deaths in Qinghai, and 6200 episodes and 66 deaths in Hainan. It was cost-effective at the $68.2/dose in private market and cost-saving at the United Nations Children’s Fund (UNICEF) recommended $25/dose for both provinces. Increasing coverage to 50% or 75% was also cost-effective. Sensitivity analyses confirmed results robustness despite parameter uncertainty. Conclusions Prioritizing PCV13 in immunization programs in Qinghai and Hainan could effectively reduce disease burden, improve population health, and promote health equity.

Prioritizing vaccine introduction to China’s National Immunization Program: a multi-criteria decision analysis

BackgroundTo prioritize the introducing of new vaccines into China’s National Immunization Program (NIP) among 10 candidate vaccines across four classes.MethodsWe developed a vaccine value framework using Multi-Criteria Decision Analysis (MCDA) to simulate the introduction of new vaccines into NIP, covering 21 criteria encompassing six dimensions: safety, effectiveness, economy, innovation, accessibility, and appropriateness. Two decision scenarios were considered: Scenario One prioritized the four classes of vaccines, while Scenario Two identified specific vaccines within each class.ResultsIn the vaccine value framework, safety received the highest weight, while innovation received the lowest. The Human Papillomavirus (HPV) vaccine was identified as a top priority for inclusion in NIP, followed by Pneumococcal Conjugate Vaccine (PCV), Haemophilus Influenzae Type B (HIB), and Rotavirus (RV) vaccines. The specific types are domestic bivalent HPV vaccine, imported 13-valent PCV vaccine, domestic HIB vaccine, and domestic RV vaccine. The results of the one-way and probabilistic sensitivity analysis demonstrated robustness.ConclusionsThis study provides a transparent, comprehensive, and quantifiable vaccine value framework to aid decision-making for introducing new vaccines into China’s NIP. According to the MCDA results, HPV should be considered the top vaccine candidate for the NIP.

Immune Response to the 13-Valent Pneumococcal Conjugate Vaccine is Reduced in Infants Immunized during the Respiratory Viral Season.

We hypothesized that response to infant pneumococcal conjugate vaccines (PCVs), administered during peak respiratory viral seasons could be blunted, particularly to higher carrier-load PCVs. We did a post-hoc analysis of a large, double-blind, randomized study comparing 13-valent vs. 7-valent PCVs (PCV13; PCV7) administered to infants (at 2, 4, 6, and 12 months). We defined respiratory viral season (RVS), based on local epidemiology as December through April and the non-RVS as June through October. Infants receiving the first dose at 7-9 weeks during the defined seasons were eligible. Serotype-specific immunoglobulin-G geometric mean concentrations (SSIgG-GMC; µg/ml) were compared between the two seasons at age seven and thirteen months. 179 and 225 infants received PCV13 in RVS and non-RVS. The corresponding numbers for PCV7 were 188 and 217. At 7 months, PCV13 recipients during RVS had significantly lower SSIgG-GMCs compared to non-RVS for 10/13 serotypes (GMC ratios 0.76-0.86). This difference remained significant in 2/13 serotypes after booster dose. Unlike PCV13 recipients, PCV7 recipients showed no seasonal difference. The results were similar for both vaccines results among children who had received the first dose only or both the first and second dose during the defined seasons. Similarly, no difference was observed if the booster was given in RVS or non-RVS. Administration of the first PCV13 dose to young infants during RVS resulted in a significant blunting of the immune response, partially corrected by booster administration. PCV7 recipients were unaffected, suggesting an increased susceptibility to respiratory viral immune blunting with higher carrier-load PCVs.

The Safety and Immunogenicity of a 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine (CRM197/TT) in Infants: A Double-Blind, Randomized, Phase III Trial.

This study aimed to evaluate the immunogenicity and safety of a 13-valent pneumococcal polysaccharide conjugate vaccine (CRM197/TT) (PCV13i) in infants. A total of 1200 infants were randomly assigned to either the experimental PCV13i group or the control PCV13 group in a 1:1 ratio. Each group received a three-dose series of the vaccine at 2, 4, and 6 months of age, followed by a booster dose at 12-15 months. Blood samples were collected before and 30 days after both primary and booster vaccinations. The primary immunogenicity endpoints were the seropositive rate and the geometric mean concentration (GMC) of IgG antibodies against the 13 pneumococcal serotypes. The primary safety endpoint was the incidence of adverse reactions within 0-7 days and 0-30 days after vaccination. Results showed that the experimental PCV13i was well tolerated, with a safety profile comparable to that of the control vaccine. Following primary vaccination, the GMCs of IgG responses against serotypes 1, 5, 6A, 6B, 14, and 18C in the experimental group were lower than those in the control group, while responses against serotypes 3, 4, 7F, 9V, 19A, 19F, and 23F were higher. The experimental group exhibited higher opsonophagocytic killing assay (OPA) geometric mean titers (GMTs) for serotypes 3, 7F, 19A, and 19F compared to the control group, while GMTs for serotypes 1, 5, 6A, and 18C were lower. Following booster vaccination, OPA GMTs of the experimental group remained higher than those of the control group for serotypes 3, 7F, and 19F, while GMTs for serotype 5 were lower. Both vaccines induced robust immune responses, with high seropositive rates and significant increases in antibody levels following vaccination. The experimental PCV13i demonstrated non-inferiority to the control PCV13 in terms of immunogenicity.

Prevention of Invasive Pneumococcal Disease Among Black or African American Children With and Without Sickle Cell Disease in the United States After Introduction of 13-Valent Pneumococcal Conjugate Vaccine, 2005 Through 2019.

Administration of pneumococcal vaccines and oral penicillin prophylaxis has been recommended for children with sickle cell disease (SCD) to reduce the risk of invasive pneumococcal disease (IPD). Characterizing changes in IPD cases among children with SCD after 13-valent pneumococcal conjugate vaccine (PCV13) introduction could help inform the need for additional prevention measures. Using data from Active Bacterial Core surveillance, we characterized IPD cases among Black or African American (Black) children aged less than 18years with SCD, non-SCD IPD risk factors, and no IPD risk factors across three time periods (pre-PCV13 [2005-2009], early-PCV13 [2010-2014], and late-PCV13 [2015-2019]), and assessed proportion of IPD cases caused by serotypes in new pneumococcal conjugate vaccines (PCV15, PCV20) recommended after 2019. We analyzed IPD incidence among children with and without SCD. From 2005 to 2019, 1725 IPD cases were reported among Black children (6.9% with SCD). IPD incidence among children with SCD declined by 50% between pre-PCV13 and late-PCV13 periods (from 332 to 167 per 100,000), although IPD incidence among children with SCD was 42 times that of children without SCD in late-PCV13 period. During late-PCV13 period, greater than 95% of IPD cases among children with SCD were non-PCV13 serotypes; PCV15/non-PCV13 and PCV20/non-PCV15 serotypes caused 19% and 22% of cases, respectively. Increase in penicillin-nonsusceptible IPD cases was not observed. Despite reductions in IPD incidence after PCV13 introduction, children with SCD are at increased risk of IPD compared to children without SCD. Use of higher valency PCVs may help reduce remaining IPD burden.

Effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in older adults

BackgroundIn 2014, the Advisory Committee on Immunization Practices recommended routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults age ≥ 65 years. Incidence of most PCV13-serotype cases declined, however serotype 3 cases have persisted. We estimated PCV13 vaccine effectiveness (VE) against PCV13-serotypes and serotype 3 invasive pneumococcal disease (IPD) among Kaiser Permanente Northern California (KPNC) adults. MethodsThis observational study included adults ≥65 years between September 1, 2014-December 31, 2020. We used active laboratory-based surveillance to identify and serotype all Streptococcus pneumoniae isolates obtained from normally-sterile sites. We estimated the odds ratio (OR) of vaccine-type IPD using conditional logistic regression stratified by age and calendar day, adjusting for sex, age, race, ethnicity, influenza vaccine receipt, 23-valent pneumococcal polysaccharide vaccine receipt since age 65, pneumonia risk factors, healthcare utilization, and KPNC service area. We estimated VEAdjusted as (1-ORAdjusted) × 100 %. ResultsThere were 610,576 adults ≥65 years in the study population. By the end of the study period, PCV13 coverage was nearly 80 %. There were 307 IPD cases during the study period, of which 98 (31.9 %) were serotype 3. PCV13 was associated with a VEAdjusted of 61.5 % (95 % CI: 36.2, 76.7; p < 0.001) against PCV13-serotype IPD and 46.3 % (95 % CI: −2.4, 77.9; p = 0.06) against serotype 3 IPD. ConclusionsPCV13 vaccination protected adults ≥65 years against IPD due to PCV13 serotypes. Continued surveillance will be critical in the ≥65-year-old population to assess the impact of higher valent PCVs on IPD serotype distribution, including individual serotypes such as serotype 3.

Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis.

Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis.

Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Effect of pneumococcal conjugate vaccination on pneumococcal carriage in hospitalised children aged 2–59 months in Mongolia: an active pneumonia surveillance programme

Data on changes in pneumococcal serotypes in hospitalised children following the introduction of the pneumococcal conjugate vaccine (PCV) in low-income and middle-income countries are scarce. In 2016, Mongolia introduced the 13-valent PCV (PCV13) into the national immunisation programme. We aimed to describe the trend and impact of PCV13 introduction on pneumococcal carriage in hospitalised children aged 2-59months with pneumonia in Mongolia over a 6-year period. In this active surveillance programme, children aged 2-59months with pneumonia who met the study case definition (cough or difficulty breathing with either respiratory rate ≥50beats per min, oxygen saturation <90%, or clinical diagnosis of severe pneumonia) were enrolled between April 1, 2015, and June 30, 2021, from four districts in Ulaanbaatar. We tested nasopharyngeal samples collected at enrolment for pneumococci using lytA real-time quantitative PCR and conducted molecular serotyping and detection of antimicrobial resistance (AMR) genes with DNA microarray. We used log-binomial regression to estimate prevalence ratios (PRs) of pneumococcal carriage, comparing prevalence in the periods before and after the introduction of PCV13 and between vaccinated and unvaccinated children for three outcomes: overall, PCV13 vaccine-type, and non-PCV13 vaccine-type carriage. PRswere adjusted with covariates that were identified by use of a directed acyclic graph, informed by relevant literature. A total of 17 688 children were enrolled, of whom 17 607 (99·5%) met the study case criteria. 6545 (42·5%) of 15 411collected nasopharyngeal swabs were tested for pneumococci. In all age groups, a similar prevalence of pneumococcal carriage was shown between the pre-PCV13 period and post-PCV13 period (882 [48·0%] of 1837 vs 2174[46·2%] of 4708; adjusted PR 0·98 [95% CI 0·92-1·04]; p=0·60). Overall, vaccine-type carriage reduced by43·6% after the introduction of PCV13 (adjusted PR 0·56 [95% CI 0·51-0·62]; p<0·0001). Younger children (aged 2-23months) showed a 47·7% reduction in vaccine-type carriage (95% CI 41·2-53·5; adjusted PR 0·52 [95% CI 0·46-0·59]; p<0·0001), whereas children aged 24-59months had a 29·3% reduction (12·6-42·8; 0·71[0·57-0·87]; p=0·0014). Prevalence of 6A, 6B, 14, 19F, and 23F decreased following the introduction of PCV13; however, 19F and 6A remained common (5·8% and 2·9%). Non-vaccine-type carriage increased (adjusted PR 1·49[95% CI 1·32-1·67]), with 15A, NT2, and 15B/C being the most prevalent serotypes. Overall, 1761 (89·3%) of 1978analysed samples contained at least one AMR gene. The percentage of samples with any AMR gene decreased with vaccine introduction (92·3% in the pre-PCV13 period vs 85·3% in the post-PCV13 period; adjusted odds ratio 0·49 [95% CI 0·34-0·70]), with similar decreases for samples with at least three AMR genes (46·8% vs 27·6%; 0·44 [0·36-0·55]). 6 years after the introduction of PCV13 in Mongolia, the prevalence of vaccine-type carriage and AMR genes showed a reduction among young hospitalised children with pneumonia. Reductions in vaccine-type carriage are likely to result in reductions in pneumococcal pneumonia. GAVI, the Vaccine Alliance.