The World Health Organization recommends vaccinating infants with pneumococcal conjugate vaccines to prevent invasive pneumococcal disease. Recent research has delved into comparing the immunogenicity and efficacy of two such vaccines: pneumococcal conjugate vaccine-10 (PCV10) and pneumococcal conjugate vaccine-13 (PCV13). This study provides a comprehensive analysis to aid in optimizing vaccination strategies and informing market access decisions.
Research Methodology
A thorough search of several databases including the Cochrane Library, EMBASE, and MEDLINE was conducted up to July 2022. The study focused on randomized trials involving children under two years of age who were administered either PCV10 or PCV13. Immunogenicity data, defined as the geometric mean ratio of serotype-specific immunoglobulin G, and seroefficacy data, represented by the relative risk of seroinfection, were collected and analyzed. The study employed both individual participant data and aggregate data where necessary.
Key Findings
From the 47 eligible studies across 38 countries, 28 provided immunogenicity data and 12 provided seroefficacy data. PCV13 showed significantly higher immunoglobulin G responses for serotypes 4, 9V, and 23F, with 1.14- to 1.54-fold increases compared to PCV10 one month after the primary vaccination series. Furthermore, the risk of seroinfection before the booster dose was lower for PCV13 for serotypes 4, 6B, 9V, 18C, and 23F. The data revealed considerable heterogeneity and inconsistency, indicating the need for careful interpretation.
Higher antibody levels post-vaccination correlated with a reduced risk of subsequent infection. Specifically, a twofold increase in antibody was linked to a 54% decrease in the risk of seroinfection. The study also employed a mathematical model to simulate the impact of introducing PCV10 and PCV13 on invasive pneumococcal disease over 25 years, revealing that PCV13 would prevent an additional 2808 cases compared to PCV10.
The insights gained from this study offer valuable information for market access decisions, particularly in choosing the most effective vaccine for public health programs.
Concrete Inferences
Key inferences from the study include:
- PCV13 provides higher immunogenicity for specific serotypes compared to PCV10.
- Lower risk of seroinfection with PCV13 supports its superior seroefficacy.
- Modeling suggests a significant long-term public health benefit of PCV13 over PCV10.
While the study underscores the benefits of PCV13, it also highlights the complexities involved in vaccine efficacy analysis due to significant heterogeneity and the limitations posed by pre-booster data. These findings emphasize the need for continued research and evaluation to optimize pneumococcal vaccination strategies and enhance market access for the most effective vaccines.
Original Article:
Health Technol Assess. 2024 Jul;28(34):1-109. doi: 10.3310/YWHA3079.
ABSTRACT
BACKGROUND: Vaccination of infants with pneumococcal conjugate vaccines is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines.
OBJECTIVES: The primary objective was to compare the immunogenicity of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. The main secondary objective was to compare the seroefficacy of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13.
METHODS: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE, ClinicalTrials.gov and trialsearch.who.int up to July 2022. Studies were eligible if they directly compared either pneumococcal conjugate vaccine-7, pneumococcal conjugate vaccine-10 or pneumococcal conjugate vaccine-13 in randomised trials of children under 2 years of age, and provided immunogenicity data for at least one time point. Individual participant data were requested and aggregate data used otherwise. Outcomes included the geometric mean ratio of serotype-specific immunoglobulin G and the relative risk 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. Each trial was analysed to obtain the log of the ratio of geometric means and its standard error. The relative risk of seroinfection (‘seroefficacy’) was estimated by comparing the proportion of participants with seroinfection between vaccine groups. The log-geometric mean ratios, log-relative risks and their standard errors constituted the input data for evidence synthesis. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis. For other serotypes, meta-analysis was used. Results from seroefficacy analyses were incorporated into a mathematical model of pneumococcal transmission dynamics to compare the differential impact of pneumococcal conjugate vaccine-10 and pneumococcal conjugate vaccine-13 introduction on invasive pneumococcal disease cases. The model estimated the impact of vaccine introduction over a 25-year time period and an economic evaluation was conducted.
RESULTS: In total, 47 studies were eligible from 38 countries. Twenty-eight and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. Geometric mean ratios comparing pneumococcal conjugate vaccine-13 versus pneumococcal conjugate vaccine-10 favoured pneumococcal conjugate vaccine-13 for serotypes 4, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher immunoglobulin G responses with pneumococcal conjugate vaccine-13. Risk of seroinfection prior to the time of booster dose was lower for pneumococcal conjugate vaccine-13 for serotype 4, 6B, 9V, 18C and 23F than for pneumococcal conjugate vaccine-10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Twofold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (relative risk 0.46, 95% confidence interval 0.23 to 0.96). In modelled scenarios, pneumococcal conjugate vaccine-13 or pneumococcal conjugate vaccine-10 introduction in 2006 resulted in a reduction in cases that was less rapid for pneumococcal conjugate vaccine-10 than for pneumococcal conjugate vaccine-13. The pneumococcal conjugate vaccine-13 programme was predicted to avoid an additional 2808 (95% confidence interval 2690 to 2925) cases of invasive pneumococcal disease compared with pneumococcal conjugate vaccine-10 introduction between 2006 and 2030.
LIMITATIONS: Analyses used data from infant vaccine studies with blood samples taken prior to a booster dose. The impact of extrapolating pre-booster efficacy to post-booster time points is unknown. Network meta-analysis models contained significant heterogeneity which may lead to bias.
CONCLUSIONS: Serotype-specific differences were found in immunogenicity and seroefficacy between pneumococcal conjugate vaccine-13 and pneumococcal conjugate vaccine-10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These methods can be used to compare the pneumococcal conjugate vaccines and optimise vaccination strategies. For future work, seroefficacy estimates can be determined for other pneumococcal vaccines, which could contribute to licensing or policy decisions for new pneumococcal vaccines.
STUDY REGISTRATION: This study is registered as PROSPERO CRD42019124580.
FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information.
PMID:39046101 | DOI:10.3310/YWHA3079
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