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

Shuo Feng; Julie McLellan; Nicola Pidduck; Nia Roberts; Julian P T Higgins; Yoon Choi; Alane Izu; Mark Jit; Shabir A Madhi; Kim Mulholland; Andrew J Pollard; Beth Temple; Merryn Voysey

doi:10.1016/j.eclinm.2023.102073

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

EClinicalMedicine. 2023 Jul 1:61:102073. doi: 10.1016/j.eclinm.2023.102073. eCollection 2023 Jul.

Authors

Shuo Feng¹, Julie McLellan², Nicola Pidduck², Nia Roberts³, Julian P T Higgins⁴, Yoon Choi⁵, Alane Izu⁶, Mark Jit⁷, Shabir A Madhi^{6

8}, Kim Mulholland^{7

9

10}, Andrew J Pollard^{1

11}, Beth Temple^{7

9

10}, Merryn Voysey^{1

11}

Affiliations

¹ Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Oxford, UK.
² Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
³ Bodleian Health Care Libraries, University of Oxford, Oxford, UK.
⁴ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁵ Modelling and Economics Unit, UK Health Security Agency, London, UK.
⁶ South African Medical Research Council MRC Vaccines and Infectious Diseases Analytics Research Unit, Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
⁸ Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ Murdoch Children's Research Institute, Melbourne, VIC, Australia.
¹⁰ Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
¹¹ NIHR Oxford Biomedical Research Centre, Oxford, UK.

Abstract

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.

Keywords: Immunogenicity; Individual participant data; Network meta-analysis; Pneumococcal conjugate vaccines; Seroefficacy.