https://orcid.org/0000-0002-6874-2161
ABSTRACT
Streptococcus pneumoniae causes a considerable disease burden among children in China. Many isolates exhibit antimicrobial resistance but are often serotypes covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Because the approved infant immunization schedule in China allows PCV13 vaccination only for those 6 weeks to 15 months of age, this phase 3 study was conducted to evaluate PCV13 immunogenicity and safety in unvaccinated older infants and children. Eligible participants were stratified by age into four cohorts: Cohort 1 (n = 125), 6 weeks−2 months; Cohort 2 (n = 354), 7−<12 months; Cohort 3 (n = 250), 1 −<2 years; Cohort 4 (n = 207), 2−<6 years. Cohort 1 received PCV13 at ages 2, 4, and 6 months; older cohorts were randomized 2:1 to PCV13 or Haemophilus influenzae type b (Hib) vaccine using age-appropriate schedules. Within-group immune responses were assessed by immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) titers. Safety evaluations included solicited reactogenicity events and adverse events (AEs). IgG geometric mean concentrations and OPA geometric mean titers for all 13 PCV13 serotypes increased for all participants vaccinated with PCV13, but not those vaccinated with Hib. Immune responses in Cohorts 2–4 were generally comparable with those in Cohort 1 (the infant series) for most serotypes. PCV13 was well tolerated across cohorts, with reported AEs consistent with expectations in these age groups; no new safety signals were identified. These results suggest that PCV13 administered as a catch-up regimen to infants and children 7 months−<6 years of age in China will effectively reduce vaccine-type pneumococcal disease in this population. NCT03574389.
Introduction
Invasive pneumococcal disease (IPD), caused by the bacterium Streptococcus pneumoniae, is a significant cause of pediatric morbidity and mortality.Citation1 An estimated 317,000 children ≤5 years of age died from pneumococcal infections in 2015 worldwide.Citation1 In addition to invasive disease (e.g., bacteremia and meningitis), noninvasive pneumococcal infections (e.g., acute otitis media [AOM], sinusitis, and bronchitis) also pose a considerable disease burden among pediatric populations.Citation2–5
Pneumococcal conjugate vaccines (PCVs) have reduced pediatric morbidity and mortality associated with S. pneumoniae.Citation1 Current World Health Organization guidelines recommend the global inclusion of PCVs in childhood immunization programs.Citation5 One such PCV is the 13-valent PCV (PCV13; Prevenar 13®, Pfizer Inc, Philadelphia, PA, USA), which is approved in >150 countries worldwide and includes saccharide conjugates for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F).Citation6,Citation7 The effectiveness of PCVs has been well demonstrated in infants and children aged 6 weeks to 5 years in other nations.Citation8,Citation9
Although pediatric deaths due to pneumococcal infections in China have decreased in recent years, a substantial disease burden remains, with an estimated 8000 pneumococcal deaths in children <6 years of age having occurred in 2017.Citation10 S. pneumoniae is also frequently identified as a cause of AOM and community-acquired pneumonia in children in China.Citation11–13 Importantly, pneumococcal isolates in China exhibit high rates of antimicrobial resistance, with a recent meta-analysis finding pooled antibiotic resistance rates among Chinese children of 74.4% to 94.4% to erythromycin, clindamycin, tetracycline, and sulfamethoxazole among >1200 pediatric IPD isolates tested against each agent.Citation14 In addition, the pooled resistance rate to penicillin and proportion of penicillin-non-susceptible S. pneumoniae were 32% and 74.6%, respectively.Citation14 Moreover, the most commonly identified serotypes were 19F (27.7%), 19A (21.2%), 14 (16.5%), 6B (8.0%), and 23F (7.3%), with an estimated 90% coverage rate of PCV13.Citation14 Findings among studies restricted to children <5 years of age were similar.Citation14 The burden of disease coupled with high rates of antimicrobial resistance and high percentages of vaccine-type disease highlight the important role of pneumococcal vaccines in controlling pediatric pneumococcal disease in China.
PCV13 was licensed in China in 2016,Citation15 and the approval is currently limited to children 6 weeks to 15 months of age, with a recommended schedule of 2, 4, and 6 months followed by a fourth injection at 12–15 months of age. Before PCV13 approval, the 7-valent PCV had been approved for children through 5 years of age.Citation16 Given the need to prevent pneumococcal disease in Chinese children younger than 6 years, it is reasonable to extend the use of PCV13 to a broader age group. Therefore, the current study was conducted to support the licensure of PCV13 in children 7 months to <6 years of age by evaluating the safety and immunogenicity of PCV13 in infants and young children from China who were naive to pneumococcal vaccination.
Methods
Study design and participants
This phase 3, randomized, open-label study evaluated the safety, tolerability, and immunogenicity of PCV13 in infants and young children at two sites in China (ClinicalTrials.gov NCT03574389; registered June 19, 2018). Enrollment commenced on June 23, 2018, and the primary completion date was August 23, 2021. Participants were stratified into four cohorts defined by their age at consent: Cohort 1, ages 6 weeks (42 days) to 2 months (56 days); Cohort 2, ages 7 months (210 days) to <12 months; Cohort 3, ages 1 to <2 years; and Cohort 4, ages 2 to <6 years. Participants in Cohort 1 received PCV13 at 2, 4, and 6 months of age (infant series), the data from which served as a licensed comparator for the other cohorts; these infants also received a toddler dose between 12 and 15 months of age. Participants in Cohorts 2, 3, and 4 were randomized 2:1 using an interactive response technology system to receive PCV13 or a control vaccine (Haemophilus influenzae type b [Hib]) according to age-appropriate schedules (Table S1). This report presents data from the primary analysis, which includes immunogenicity data through 1 month after the infant series (Cohort 1) or last vaccination (Cohorts 2, 3, and 4) and safety data through 1 month after the infant series (Cohort 1) or 6 months after the last vaccination (Cohorts 2, 3, and 4). Additional data from later time points for Cohort 1 will be reported separately.
Eligible participants were healthy infants and children, as determined by their medical history, physical examination, and investigator judgment, who were 6 weeks to <6 years of age. Key exclusion criteria included previous receipt of pneumococcal or Hib vaccine, known or suspected immune deficiency or suppression, or history of culture-proven IPD.
During the study, non-study vaccinations were permitted ≥4 days before and ≥7 days after study vaccination, except for bacillus Calmette-Guérin and oral vaccines, which were permitted at any time. Hib vaccination was considered a non-study vaccine in the PCV13 arms. The open-label study design prevented accidental overdosing of the Hib vaccine to participants of the Hib arm. No pneumococcal vaccines (licensed or investigational), other than the study vaccine, were permitted during the study.
The study was conducted in accordance with the International Ethical Guidelines for Biomedical Research Involving Human Subjects, the International Conference on Harmonisation Guideline for Good Clinical Practice, and the Declaration of Helsinki. Written informed consent was obtained from each participant’s parent or guardian before beginning any study-related activity.
Interventions
Participants received intramuscular injections of PCV13 or Hib vaccine into the left anterolateral thigh muscle or left deltoid at vaccination visits. Each 0.5-mL dose of PCV13 contains 2.2 µg of saccharides from pneumococcal serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, and 23F and 4.4 µg of serotype 6B saccharides, each individually conjugated to cross-reactive material 197. Hib vaccine, used here as a control, is indicated for active immunization for the prevention of invasive disease caused by Haemophilus influenzae type b. It was chosen because in China, the dosing schedules of Hib and PCV13 for a given age group are very similar, and because it has a well-known safety profile.
Objectives, endpoints, and assessments
Immunogenicity
The primary immunogenicity objective was to describe the immune responses to PCV13 in Cohorts 2, 3, and 4 at 1 month after the last dose and those in Cohort 1 at 1 month after the infant series, as measured by immunoglobulin G (IgG) geometric mean concentrations (GMCs) for each of the PCV13 serotypes. Secondary immunogenicity endpoints included a similar evaluation for opsonophagocytic activity (OPA) geometric mean titers (GMTs); a summary of IgG GMCs and OPA GMTs among PCV13 and Hib vaccine recipients in each of Cohorts 2, 3, and 4; and an evaluation of IgG GMCs and OPA GMTs in Cohort 1. OPA titers were determined in a randomly selected subset of approximately 50 PCV13 recipients in each cohort, and approximately 25 Hib vaccine recipients in Cohorts 2, 3, and 4. IgG GMCs are a measure of the concentration of antibody, while OPA titers are a measure of functional antibody responses.
Immunogenicity evaluations were based on blood draws performed before the first vaccination (baseline) for all participants and at a) 1 month after the infant vaccination for Cohort 1 or b) 1 month after the last vaccination for Cohorts 2, 3, and 4.
Safety
The primary safety objective was to evaluate the safety profile of PCV13 in Cohorts 2, 3, and 4; PCV13 had already been licensed for use in 6- to 8-week-old infants (i.e., Cohort 1) and thus has a known safety profile for that cohort. Corresponding endpoints included percentages of participants with prespecified local reactions (redness, swelling, and tenderness) and systemic events (fever [all cohorts]; decreased appetite, drowsiness, and irritability [Cohorts 2 and 3]; fatigue, headache, vomiting, diarrhea, muscle pain, and joint pain [Cohort 4]), including antipyretic use, in the 7 days after each dose. Adverse events (AEs) were assessed up to 1 month after the last vaccination; serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) were assessed through 6 months after the last dose. AEs, SAEs, and NDCMCs were evaluated through 1 month after either Dose 3 (AEs, the final dose of the infant series) or Dose 4 (SAEs, NDCMCs) in Cohort 1 as secondary safety endpoints.
Local reactions and systemic events were monitored by each participant’s caregiver using an electronic diary and graded by severity using a specified grading scale (Table S2). Information regarding AEs was obtained by study investigators through direct observation or through communication with participants’ parent(s)/legal guardian(s).
Analyses
Sample size
The study planned to enroll 125 participants in Cohort 1 and 177 participants in each of Cohorts 2, 3, and 4 for a total of 656 participants. Because the study was descriptive, there was no formal hypothesis testing performed.
Immunogenicity
The evaluable immunogenicity population served as the primary population for immunogenicity analyses and included all eligible participants who received all study vaccinations required for their study cohort (i.e., three infant doses for Cohort 1), had blood drawn for assay testing within the prespecified period, had valid assay results for the proposed analysis, receive no prohibited vaccine, and had no major protocol violations. The evaluable immunogenicity population was used to assess serotype-specific IgG GMCs. A smaller, randomly selected subset of the evaluable immunogenicity population (described in Immunogenicity under Objectives, endpoints, and assessments) was used to measure OPA titers.
For IgG GMCs and OPA GMTs, 95% CIs were calculated by back transformation of the CIs for the mean of the logarithmically transformed GMC or GMT using a Student’s t distribution. Other immunogenicity evaluations included percentages of participants with IgG concentrations ≥0.35 µg/mL and OPA titers at or greater than the lower limit of quantitation (LLOQ; 1:8 for each serotype), for which 95% CIs were calculated using the Clopper and Pearson method. Additionally, geometric mean fold rises (GMFRs) in IgG and OPA from baseline to after vaccination were calculated for each group, with 95% CIs calculated by back transformation of the CIs for the mean logarithm of the fold rises using a Student’s t distribution.
Safety
Safety analyses were based on the safety population, which included all participants who received ≥1 dose of investigational product. For Cohorts 2, 3, and 4, randomized participants who received the wrong vaccine were included in the safety analyses based on the vaccine they received. AEs and SAEs were categorized according to the Medical Dictionary for Regulatory Activities.
Results
Participants
A total of 656 participants were initially enrolled (125 in Cohort 1 and 177 in each of Cohorts 2, 3, and 4). After enrollment was complete, it was noted that 280 participants were enrolled from immunization clinics whose eligibility to participate in clinical trials was not clear due to ambiguity in the interpretation of local policies. To ensure that the planned sample size was used, an additional 280 participants (177, 73, and 30 in Cohorts 2, 3, and 4, respectively) were recruited at a different study site (Guanyun, ~80 km from the previous study site). On completion of the study, examination of the data from the original 280 participants found no issues regarding participant safety or data quality and integrity. Thus, all reported data include both the original and additional 280 participants enrolled in the study.
Including the additional 280 participants, 936 participants (125, 354, 250, and 207 in Cohorts 1, 2, 3, and 4, respectively) were randomized and 932 received investigational product (). The respective completion rates for vaccination and the postvaccination blood draw visit were 73.6%, 84.2%, 85.2%, and 95.7%. Across all cohorts, the most common reason for withdrawal was withdrawal by parent/guardian. The relatively high withdrawal rate in Cohort 1 was attributed to an incident in January 2019, unrelated to the current study, in which 145 infants and children received expired poliomyelitis vaccine at a regional vaccination center in the same province where the study was being conducted. This led public health officials to temporarily halt all vaccinations, including those of the study participants, and resulted in a general lack of confidence in vaccination and withdrawals from the study.
Figure 1. Participant disposition in (a) Cohort 1 (participants 42–56 days of age at Dose 1), (b) Cohort 2 (participants 7–<12 months of age at Dose 1), (c) Cohort 3 (participants 1–<2 years of age at Dose 1), and (d) Cohort 4 (participants 2–<6 years of age at Dose 1).
All participants were Asian, with a slightly higher percentage of male participants (). Demographic characteristics between PCV13 and Hib vaccine groups were similar except for a greater percentage of female participants in the Cohort 4 Hib vaccine group.
Table 1. Participant demographics.
Immunogenicity
Cohort 2
In the Cohort 2 PCV13 group (evaluable immunogenicity population, n = 176), serotype-specific IgG GMCs ranged from 0.01 µg/mL (serotypes 4 and 18C) to 0.38 µg/mL (serotype 5) at baseline and 1.19 (serotype 3) to 10.89 (serotype 14) µg/mL at 1 month after the vaccination series; corresponding GMFRs ranged from 8.0 (serotype 5) to 389.1 (serotype 14; ). Also, at 1 month after the vaccination series, ≥95.5% of participants had IgG concentrations ≥0.35 µg/mL for each of the serotypes (Figure S1A). IgG GMCs remained low for all serotypes in the Hib vaccine group (n = 72) ().
Figure 2. PCV13 serotype-specific IgG GMCs 1 month after the infant series (Cohort 1) or 1 month after the last dose (Cohorts 2, 3, and 4) and GMFRs from baseline to 1 month after the last vaccination.
Serotype-specific OPA GMTs also rose in the Cohort 2 PCV13 group (subset of the evaluable immunogenicity population, n = 87), with GMFRs from baseline to 1 month after the vaccination series ranging from 34.5 (serotype 1) to 1208.5 (serotype 6A); these GMTs were well differentiated and substantially higher than those in the Hib vaccine group (n = 34) (). Also, at 1 month after the vaccination series, ≥94.3% of participants had OPA titers ≥LLOQ for each of the serotypes (Figure S1B).
Figure 3. PCV13 serotype-specific OPA GMTs 1 month after the infant series (Cohort 1) or 1 month after the last dose (Cohorts 2, 3, and 4) and GMFRs from baseline to 1 month after the last vaccination.
Cohort 3
In the Cohort 3 PCV13 group (n = 127), serotype-specific IgG GMCs ranged from 0.03 µg/mL (serotypes 4 and 14) to 0.69 µg/mL (serotype 5) at baseline, and 1.32 (serotype 3) to 9.79 (serotype 14) µg/mL at 1 month after the vaccination series; corresponding GMFRs ranged from 3.7 (serotype 5) to 282.9 (serotype 14; ). Also, at 1 month after the vaccination series, ≥94.5% of participants had IgG concentrations ≥0.35 µg/mL for each of the serotypes (Figure S1A). IgG GMCs remained low for all serotypes in the Hib vaccine group (n = 77) ().
Serotype-specific OPA GMTs also rose in the Cohort 3 PCV13 group (n = 78), with GMFRs from baseline to 1 month after the vaccination series ranging from 23.3 (serotype 1) to 1104.0 (serotype 6A); these GMTs were well differentiated and substantially higher than those in the Hib vaccine group (n = 42) (). Also, at 1 month after the vaccination series, ≥96.2% of participants had OPA titers ≥LLOQ for each of the serotypes (Figure S1B).
Cohort 4
In the Cohort 4 PCV13 group (n = 131), serotype-specific IgG GMCs ranged from 0.07 µg/mL (serotype 4) to 1.72 µg/mL (serotype 19A) at baseline and 1.12 (serotype 3) to 11.62 (serotype 19A) µg/mL at 1 month after vaccination; corresponding GMFRs ranged from 2.8 (serotype 5) to 62.5 (serotype 4; ). Also, at 1 month after vaccination, ≥96.9% of participants had IgG concentrations ≥0.35 µg/mL for each of the serotypes (Figure S1A). IgG GMCs remained low for all serotypes in the Hib vaccine group (n = 67) ().
Serotype-specific OPA GMTs also rose in the Cohort 4 PCV13 group (n = 71), with GMFRs from baseline to 1 month after vaccination ranging from 9.0 (serotypes 1 and 3) to 180.7 (serotype 4); these GMTs were well differentiated and substantially higher than those in the Hib vaccine group (n = 36) (). Also, at 1 month after vaccination, ≥95.8% of participants had OPA titers ≥LLOQ for each of the serotypes (Figure S1B).
Cohort 1
Serotype-specific IgG immune responses measured 1 month after the infant PCV13 series (n = 72) in Cohort 1 are shown for comparison in and Figure S1A. OPA results (n = 37) are shown in and Figure S1B.
Safety
Local reactions
In accordance with the primary safety objectives, local reactions were not assessed for Cohort 1. Local reactions were reported by 28.0%, 9.1%, and 2.1% of participants in the Cohort 2 PCV13 group (n = 236) within 7 days after Doses 1, 2, and 3, respectively (). In the Hib vaccine group (n = 117), percentages were comparatively lower after Dose 1 and higher after Dose 2. In the Cohort 3 PCV13 group (n = 164), local reactions were reported by 27.4% and 6.2% of participants within 7 days after Doses 1 and 2, respectively (). Percentages were generally lower in the Hib vaccine group (n = 83) in comparison after Dose 1. In the Cohort 4 PCV13 group (n = 138), 34.8% of participants reported local reactions within 7 days after vaccination, with percentages generally similar among Hib vaccine recipients (n = 67) ().
Figure 4. Percentage of participants with local reactions within 7 days after each dose in (a) Cohort 2, (b) Cohort 3, and (c) Cohort 4.
Redness was the most commonly reported local reaction across Cohorts 2, 3, and 4, and most local reactions were mild or moderate in severity. The median onset of local reactions in Cohorts 2, 3, and 4 was 1–2 days following each dose of PCV13 or Hib vaccine, and the median duration of local reactions following each dose was ≤2 days.
Systemic events
In accordance with the primary safety objectives, systemic events were not assessed for Cohort 1. Systemic events were reported by 9.7%, 10.5%, and 0.5% of participants in the Cohort 2 PCV13 group (n = 236) within 7 days after Doses 1, 2, and 3, respectively (). In the Cohort 2 Hib vaccine group (n = 117), percentages were generally similar after Dose 1 and numerically lower after Dose 2. In the Cohort 3 PCV13 group (n = 164), systemic events were reported by 15.9% and 2.7% of participants within 7 days after Doses 1 and 2, respectively (). Percentages of participants reporting systemic events were numerically lower in the Cohort 3 Hib vaccine group (n = 83), with the exception of drowsiness after Dose 1. In the Cohort 4 PCV13 group (n = 138), 12.3% of participants reported systemic events within 7 days after vaccination, with percentages slightly higher among Hib vaccine recipients (n = 68) ().
Figure 5. Percentage of participants with systemic events within 7 days after each dose in (a) Cohort 2, (b) Cohort 3, and (c) Cohort 4.
Fever was the most commonly reported systemic event across Cohorts 2, 3, and 4 (≤10.4% per group after each dose), with the addition of decreased appetite (Cohort 3) and fatigue (Cohort 4). Most systemic events were mild in severity; no temperatures >40.0°C were reported. The median onset of systemic events in Cohorts 2, 3, and 4 was 1–4 days following each dose of PCV13 or Hib vaccine, and the median duration of systemic events following each dose was 1–6 days. Antipyretic use was generally low (≤12.2% across these cohorts) after any dose.
Adverse events
In Cohorts 2, 3, and 4, percentages of participants reporting any AEs through 1 month after the last dose were higher in the PCV13 groups (32.2% [n = 236], 12.7% [n = 165], and 8.0% [n = 138], respectively) than in the Hib vaccine groups (24.8% [n = 117], 1.2% [n = 83], and 1.5% [n = 68]; ).
Table 2. Summary of AEs reported from the signing of informed consent document through 1 month after the infant series (Cohort 1) or 1 month after the last dose (Cohorts 2, 3, and 4)a.
In Cohort 2, reported AEs were most commonly categorized as respiratory, thoracic, and mediastinal disorders (PCV13, 16.1%; Hib, 12.0%) or general disorders and administrative site conditions (PCV13, 14.4%; Hib, 11.1%). The most frequently reported individual AE was pyrexia (PCV13, 14.4%; Hib, 11.1%). Most reported AEs were mild to moderate in severity; severe pyrexia was reported by eight and seven participants in the PCV13 and Hib vaccine groups, respectively, and severe upper respiratory tract infection was reported by one participant in each group. Few participants in Cohort 2 (PCV13, 2.1%; Hib, 0.9%) reported SAEs through 6 months after the last dose; of these, 3 SAEs of pyrexia, one of which led to study withdrawal, were considered related to PCV13.
Adverse event profiles in Cohorts 3 and 4 were similar. In both cohorts, reported AEs were most commonly categorized as general disorders and administrative site conditions (PCV13, ≤4.8%; Hib, ≤1.2%); respiratory, thoracic, and mediastinal disorders (PCV13, ≤3.6%; Hib, 0%); and infections and infestations (PCV13, ≤3.0%; Hib, ≤1.5%). The most frequently reported individual AEs were pyrexia (PCV13, ≤4.8%; Hib, ≤1.2%), cough (PCV13, ≤3.0%; Hib, 0%), and nasopharyngitis (PCV13, ≤2.2%; Hib, ≤1.5%). Most reported AEs were mild to moderate in severity; severe pyrexia, hand-foot-and-mouth disease, and bronchitis were all reported by one participant in the Cohort 3 PCV13 group. None of the SAEs reported through 6 months after the last dose (Cohort 3, 3 SAEs reported by two participants; Cohort 4, 5 SAEs reported by three participants) were considered treatment related.
In Cohort 1 (n = 125), 11.2% of participants reported any AEs through 1 month after the infant series (). Reported AEs were most commonly categorized as infections and infestations (7.2% of participants), and the most frequently reported individual AE was upper respiratory tract infection (3.2%). Most reported AEs were mild in severity; no severe AEs were reported. None of the four SAEs reported through 1 month after the infant series in Cohort 1 were considered treatment related.
No participants reported NDCMCs during the study period.
Discussion
This study demonstrated that PCV13, given as a catch-up regimen in pediatric age groups 7 to <12 months, 1 to <2 years, and 2 to <6 years in China elicited robust functional immune responses to the PCV13 serotypes. Substantial increases in IgG GMCs and OPA GMTs at 1 month after the last vaccination were observed in all older age groups for all PCV13 serotypes, and ≥94% of participants had IgG concentrations ≥0.35 µg/mL or OPA titers ≥LLOQ at this time point. Antibody responses were generally higher among older children, despite participants in these groups receiving fewer PCV13 doses, likely reflecting greater immune maturity in older children.Citation17 PCV13 was well tolerated in the age groups evaluated, and reported AEs were typical of medical events or conditions common in these age groups. No new safety signals were identified during the study. Collectively, these study results indicate that PCV13 will be safe and effective in Chinese infants and children <6 years of age.
In addition to infants, young children in various global regions remain at increased risk of IPD.Citation18–23 In China, approximately 70% of patients <5 years of age diagnosed with IPD at a single children’s hospital during 2010–2017 were 1–<5 years of age, and IPD hospitalization rates were 11.2 and 13.3 per 100,000 among children 1–<2 and 2 − <5 years of age, respectively.Citation24 A similar study found that among children of all ages who were diagnosed with IPD during 2008–2017 within the pediatric departments of two other Chinese hospitals, more than half were 1 − 5 years of age.Citation25 More broadly, pneumonia was responsible for 7.6% of deaths among Chinese children 1 − 4 years of age in 2015.Citation26
Epidemiologic studies from global regions outside of China have demonstrated that implementation of national PCV infant programs is associated with substantial reductions in pneumococcal disease among young children.Citation18–23 However, PCV13 uptake using the licensed infant schedule in China has been low,Citation27 and vaccination of young (<6 years) children who went unvaccinated as infants may be an alternative approach for protecting this age group against pneumococcal disease. A study in Taiwan showed that a PCV13 catch-up program targeting children 2–5 years of age led to a 69% reduction in IPD rates among children ≤5 years of age.Citation28
In addition to providing direct protection against disease, vaccination of younger children may interrupt pneumococcal transmission to other age groups. Nasopharyngeal carriage of S. pneumoniae is a prerequisite for pneumococcal transmission, and, ultimately, disease.Citation29 Implementation of PCV vaccination programs is associated with reductions in pediatric nasopharyngeal carriageCitation30,Citation31 and marked decreases in pneumococcal disease among both targeted and non-targeted age groups.Citation32 As such, vaccination of young children in China with PCV13 may have substantial indirect effects on disease rates in other age groups, particularly given the high rate of invasive disease caused by PCV13 serotypes in China.Citation14
Study limitations include potential bias resulting from the open-label design. Additionally, the findings may not be generalizable to populations outside of China. It should be noted that while this study was a descriptive study without strict hypothesis testing, it was designed similarly to other studies evaluating use of PCV13 in children past infancy.Citation33,Citation34
Conclusion
In this study, PCV13 administered as a catch-up regimen to infants and children 7 months to <6 years of age in China was safe and elicited robust and functional immune responses to all PCV13 serotypes. These findings support the expectation that PCV13 will effectively prevent vaccine-type pneumococcal disease in this population.
Data sharing statement
Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.
Supplemental Material
Download PDF (335.8 KB)Acknowledgments
The authors thank the colleagues from National Institutes for Food and Drug Control (NIFDC) who conducted the immunogenicity testing for this study, they are: Qiang Ye, Jiangjiao Li, Hong Li, Xiao Xu, Gang Shi, Wenbin Liu, Lina Guo, Rufeng Liu, Kang Li, Yang Huang, Huijing Du. Editorial/medical writing support was provided by Judith Kandel, PhD, of ICON (Blue Bell, PA) and was funded by Pfizer Inc.
Disclosure statement
KC, YH, HP, JW, and DZ report no conflicts of interest. All other authors are employees of Pfizer and may hold stock or stock options.
Supplementary data
Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2235926.
Additional information
Funding
References
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