Understanding healthcare providers' preferred attributes of pediatric pneumococcal conjugate vaccines in the United States.

As higher-valent pneumococcal conjugate vaccines (PCVs) become available for pediatric populations in the US, it is important to understand healthcare provider (HCP) preferences for and acceptability of PCVs. US HCPs (pediatricians, family medicine physicians and advanced practitioners) completed an online, cross-sectional survey between March and April 2023. HCPs were eligible if they recommended or prescribed vaccines to children age <24 months, spent ≥25% of their time in direct patient care, and had ≥2 y of experience in their profession. The survey included a discrete choice experiment (DCE) in which HCPs selected preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes. Relative attribute importance was quantified. Among 548 HCP respondents, the median age was 43.2 y, and the majority were male (57.9%) and practiced in urban areas (69.7%). DCE results showed that attributes with the greatest impact on HCP decision-making were 1) immune response for the shared serotypes covered by PCV13 (31.4%), 2) percent of invasive pneumococcal disease (IPD) covered by vaccine serotypes (21.3%), 3) acute otitis media (AOM) label indication (20.3%), 4) effectiveness against serotype 3 (17.6%), and 5) number of serotypes in the vaccine (9.5%). Among US HCPs, the most important attribute of PCVs was comparability of immune response for PCV13 shared serotypes, while the number of serotypes was least important. Findings suggest new PCVs eliciting high immune responses for serotypes that contribute substantially to IPD burden and maintaining immunogenicity against serotypes in existing PCVs are preferred by HCPs.

Estimated population-level impact of pneumococcal conjugate vaccines against all-cause pneumonia mortality among unvaccinated age groups in five Latin American countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multi-country study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. METHODS: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000-2019, with 1,795,789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the post-vaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. RESULTS: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among ≥65 years in Chile. DISCUSSION: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Nurses' preferences regarding MenACWY conjugate vaccines attributes: a discrete choice experiment in Spain.

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.

Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13.

Introduction: Pneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx. Methods: Following introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays. Results: The prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load. Discussion: We conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania.

[After the COVID-19 pandemic-Which new vaccinations for adults are available or coming soon?] / Nach der COVID-19-Pandemie ­ welche neuen Impfungen im Erwachsenenalter sind schon oder bald verfügbar?

The accumulation of respiratory infections in the winter months repeatedly highlights the relevance of prevention through vaccination, even beyond a pandemic. Current developments in this field are therefore highly relevant, particularly for older people who are more susceptible to infections due to immune senescence and comorbidities. The Standing Committee on Vaccination (STIKO) has responded accordingly by recommending the 20-valent pneumococcal conjugate vaccine PCV20 for standard and indication vaccination of adults. Furthermore, new vaccines against respiratory syncytial virus (RSV) infections are available for which the STIKO has not yet issued a recommendation. The development of other more effective and more immunogenic vac2cines is being driven in particular by new technologies, such as mRNA or vector vaccines. Various higher valent pneumococcal vaccine candidates and, for example, universal influenza vaccines are also already in development.

Accelerating Pneumococcal Conjugate Vaccine introductions in Indonesia: key learnings from 2017 to 2022.

Despite high pneumococcal disease and economic burden in Indonesia and interest to introduce pneumococcal conjugate vaccine (PCV), there were challenges in establishing a comprehensive strategy to accelerate and enable the introduction in country in the early 2010s. Starting in 2017, Clinton Health Access Initiative and partners supported the government of Indonesia with evidence-based decision-making and implementation support for introducing PCV into the routine immunization program. Indonesia has since accelerated PCV roll out, with nationwide reach achieved in 2022. On the path to PCV introduction, several challenges were observed that impacted decision making on whether and on how to optimally roll out PCV, resulting in significant introduction delays; including (1) a complex country context with a devolved government structure, fragmented domestic funding streams, and an imminent transition out of major immunization donor (Gavi) support; (2) strong preference to use domestically sourced products, with limited experience accessing global pooled procurement mechanism including for vaccines; and (3) concerns around programmatic feasibility and sustainability. This case study documents key insights into the challenges experienced and how those were systematically addressed to accelerate new vaccine introduction in Indonesia, with support from local and global stakeholders over time. The learnings would be beneficial for other countries yet to introduce critical new vaccines, in particular those with similar archetype as Indonesia e.g., middle-income countries with domestic manufacturing capacity and/or countries recently transitioning out of Gavi support.

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

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

Health and economic outcomes of 20-valent pneumococcal conjugate vaccine compared to 15-valent pneumococcal conjugate vaccine strategies for adults in Greece.

Objective: Higher valency pneumococcal conjugate vaccines (PCVs) are expected to improve protection against pneumococcal disease through coverage of additional serotypes. The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 15-valent pneumococcal conjugate vaccine (PCV15) alone or followed by 23-valent polysaccharide vaccine (PPV23) for adults in Greece. Methods: A published Markov model was adapted to simulate lifetime risk of clinical and economic outcomes from the public payer's perspective. The model population was stratified based on age and risk profile (i.e., low, moderate, or high-risk of developing pneumococcal disease). Epidemiologic parameters, serotype coverage and vaccines' effectiveness were based on published literature, while direct medical costs (prices €, 2022) were obtained from official sources. Main model outcomes were projected number of invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP) cases and attributable deaths, costs and quality-adjusted life-years (QALY) for each vaccination strategy. Sensitivity analyses were performed to ascertain the robustness of model results. Results: Over the modeled time horizon, vaccination with PCV20 compared to PCV15 alone or PCV15 followed by PPV23 prevents an additional 747 and 646 cases of IPD, 10,334 and 10,342 cases of NBP and 468 and 455 deaths respectively, resulting in incremental gain of 1,594 and 1,536 QALYs and cost savings of €11,183 and €48,858, respectively. PSA revealed that the probability of PCV20 being cost-effective at the predetermined threshold of €34,000 per QALY gained was 100% compared to either PCV15 alone or the combination of PCV15 followed by PPV23. Conclusion: PCV20 is estimated to improve public health by averting additional pneumococcal disease cases and deaths relative to PCV15 alone or followed by PPV23, and therefore translates to cost-savings for the public payer. Overall results showed that vaccination with PCV20 was estimated to be a dominant vaccination strategy (improved health outcomes with reduced costs) over PCV15 alone or followed by PPV23 for prevention of pneumococcal disease in adults in Greece.

Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.

Objectives: To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period. Methods: All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines. Results: Overall, 1,516 S. pneumoniae isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years. Conclusion: PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.

Heterologous Expression of Recombinant Proteins and Their Derivatives Used as Carriers for Conjugate Vaccines.

Carrier proteins that provide an effective and long-term immune response to weak antigens has become a real breakthrough in the disease prevention, making it available to a wider range of patients and making it possible to obtain reliable vaccines against a variety of pathogens. Currently, research is continuing both to identify new peptides, proteins, and their complexes potentially suitable for use as carriers, and to develop new methods for isolation, purification, and conjugation of already known and well-established proteins. The use of recombinant proteins has a number of advantages over isolation from natural sources, such as simpler cultivation of the host organism, the possibility of modifying genetic constructs, use of numerous promoter variants, signal sequences, and other regulatory elements. This review is devoted to the methods of obtaining both traditional and new recombinant proteins and their derivatives already being used or potentially suitable for use as carrier proteins in conjugate vaccines.

Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to Higher-Valent Options in Greek Infants.

In June 2010, Greece introduced the 13-valent pneumococcal conjugate vaccine (PCV13) for pediatric vaccination and has since observed a large decrease in pneumococcal disease caused by these vaccine serotypes, yet the disease prevalence of non-vaccine serotypes has increased. Two higher-valent conjugate vaccines, a 15-valent (PCV15) and a 20-valent (PCV20), were developed to improve serotype coverage and combat serotype replacement. A decision-analytic model was adapted to the Greek setting using historical pneumococcal disease trends from PCV13 to forecast future clinical and economic outcomes of higher-valent PCVs over a 10-year period (2023-2033). The model estimated outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and otitis media (OM) resulting from a switch in vaccination programs to PCV15 in 2023 or switching to PCV20 in 2024. Cost-effectiveness was evaluated from the third-party payer's perspective in the Greek healthcare system. Compared to implementing PCV15 one year earlier, switching from PCV13 to PCV20 in 2024 was estimated to be a cost-saving strategy by saving the Greek health system over EUR 50 million in direct medical costs and averting over 250 IPD cases, 54,800 OM cases, 8450 pneumonia cases, and 255 deaths across all ages over a 10-year period.

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies.

BACKGROUND: Neither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines. METHODS: We collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated. RESULTS: Among 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes. CONCLUSIONS: Vaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.

Dynamics of Pediatric Antibiotic Use Differ between High- and Low-Prescribing Clinics after Pneumococcal Conjugate Vaccines.

OBJECTIVE: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age. METHODS: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated. RESULTS: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]). CONCLUSIONS: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.

Development of a novel glycoengineering platform for the rapid production of conjugate vaccines.

Conjugate vaccines produced either by chemical or biologically conjugation have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccine assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel biotechnological platform that overcomes the limitations of the current conjugate vaccine design method(s). As a model, we focused our design on a leading bioconjugation method using N-oligosaccharyltransferase (OTase), PglB. The installation of MAGIC led to at least twofold increase in glycoconjugate yield via MAGIC when compared to conventional N-OTase based bioconjugation method(s). Then, we improved MAGIC to (a) allow rapid installation of glycoengineering component(s), (b) omit the usage of antibiotics, (c) reduce the dependence on protein induction agents. Furthermore, we show the modularity of the MAGIC platform in performing glycoengineering in bacterial species that are less genetically tractable than the commonly used Escherichia coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against serious bacterial pathogens. We anticipate the utility of the MAGIC platform could enhance vaccines production due to its compatibility with virtually any bioconjugation method, thus expanding vaccine biopreparedness toolbox.

Worldwide Index of Serotype-Specific Pneumococcal Antibody Responses (WISSPAR): A curated database of clinical trial data.

The Worldwide Index of Serotype Specific Pneumococcal Antibody Responses (WISSPAR; https://wisspar.com), is a centralized, online platform housing data on immunogenicity from clinical trials of pneumococcal vaccines. The data on WISSPAR are primarily curated from outcomes tables from clinical trials and are made available in a searchable format that can be readily used for downstream analyses. The WISSPAR database includes trials covering numerous vaccine products, manufacturers, dosing schedules, age groups, immunocompromised groups, and geographic regions. Customizable data visualization tools are embedded within the site, or the data can be exported for further analyses. Users can also browse summary information about the clinical trials and their results. WISSPAR provides a platform for analysts and policy makers to efficiently gather, compare, and collate clinical trial data about pneumococcal vaccines.

Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data.

Background: Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods: In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. Findings: 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96). Interpretation: Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. Funding: The NIHR Health Technology Assessment Programme.

Highly Resistant Serotype 19A Streptococcus pneumoniae of the GPSC1/CC320 Clone from Invasive Infections in Poland Prior to Antipneumococcal Vaccination of Children.

INTRODUCTION: The introduction of pneumococcal conjugate vaccines (PCV) into the national immunization programs (NIPs) has significantly reduced the number of pneumococcal infections. However, infections caused by isolates of non-vaccine serotypes (NVT) started spreading shortly thereafter and strains of NVT 19A have become the main cause of invasive pneumococcal disease burden worldwide. The aim of the study was to characterize serotype 19A invasive pneumococci of GPSC1/CC320 circulating in Poland before the introduction of PCV into the Polish NIP in 2017 and to compare them to isolates from other countries where PCVs were implemented much earlier than in Poland. METHODS: All the GPSC1/CC320 isolates were analyzed by serotyping, susceptibility testing, and whole genome sequencing followed by analyses of resistome, virulome, and core genome multilocus sequence typing (cgMLST), including comparative analysis with isolates with publicly accessible genomic sequences (PubMLST). RESULTS: During continuous surveillance the NRCBM collected 4237 invasive Streptococcus pneumoniae isolates between 1997 and 2016, including 200 isolates (4.7%) of serotype 19A. The most prevalent among 19A pneumococci were highly resistant representatives of Global Pneumococcal Sequence Cluster 1/Clonal Complex 320, GPSC1/CC320 (n = 97, 48.5%). Isolates of GPSC1/CC320 belonged to three sequence types (STs): ST320 (75.2%) ST4768 (23.7%), and ST15047 (1.0%), which all represented the 19A-III cps subtype and had complete loci for both PI-1 and PI-2 pili types. On the basis of the cgMLST analysis the majority of Polish GPSC1/CC320 isolates formed a group clearly distinct from pneumococci of this clone observed in other countries. CONCLUSION: Before introduction of PCV in the Polish NIP we noticed an unexpected increase of serotype 19A in invasive pneumococcal infections, with the most common being representatives of highly drug-resistant GPSC1/CC320 clone, rarely identified in Europe both before and even after PCV introduction.

Spread of multidrug resistance in non-PCV13/PCV20 serotypes of Streptococcus pneumoniae: A cross-sectional study ten years after the introduction of pneumococcal conjugate vaccine in Japan.

Ten years after the introduction of the pneumococcal conjugate vaccine (PCV) in Japan, the prevalence rates of non-PCV13 and non-PCV20 serotypes among pediatric pneumococcal isolates were 94.0% and 73.7%, respectively. The predominant non-PCV13/PCV20 serotypes (15A, 35B, and 23A) were mostly multidrug-resistant (≥80.5%), exhibiting non-susceptibility to penicillin.

Safety and immunogenicity of quadrivalent meningococcal polysaccharide vaccine (MPV ACYW135) compared with quadrivalent meningococcal conjugate vaccine (Menactra®) in Malian children.

Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups (P > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar (P > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups (P > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2-10 years.Clinical Trial Registration: NCT04450498.