Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study
Abstract
Background Efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) was inferred before licensure from an aggregate correlate of protection established for the seven-valent vaccine (PCV7). We did a postlicensure assessment of serotype-specific vaccine effectiveness and immunogenicity in England, Wales, and Northern Ireland to derive the correlates of protection for individual serotypes.Methods We assessed vaccine effectiveness against invasive pneumococcal disease using the indirect cohort method. We measured serotype-specific IgG concentration in infants after they were given two priming doses of PCV7 (n=126) or PCV13 (n=237) and opsonophagocytic antibody titre from a subset of these infants (n=100). We derived correlates of protection by relating percentage protection to a threshold antibody concentration achieved by an equivalent percentage of infants. We used multivariable logistic regression to estimate vaccine effectiveness and reverse cumulative distribution curves to estimate correlates of protection.Findings For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58-84). Vaccine effectiveness was 90% (34-98) for the PCV7 serotypes and 73% (55-84) for the six additional serotypes included in PCV13. Protection was shown for four of the six additional PCV13 serotypes (vaccine effectiveness for serotype 3 was not significant and no cases of serotype 5 infection occurred during the observation period). The vaccine effectiveness for PCV13 and PCV7 was lower than predicted by the aggregate correlate of protection of 0·35 μg/mL used during licensing. Calculated serotype-specific correlates of protection were higher than 0·35 μg/mL for serotypes 1, 3, 7F, 19A, 19F, and lower than 0·35 μg/mL for serotypes 6A, 6B, 18C, and 23F. Opsonophagocytic antibody titres of 1 in 8 or higher did not predict protection.Interpretation PCV13 provides significant protection for most of the vaccine serotypes. Although use of the aggregate correlate of protection of 0·35 μg/mL has enabled the licensing of effective new PCVs, serotype-specific correlates of protection vary widely. The relation between IgG concentration after priming and long-term protection needs to be better understood.Funding Public Health England and UK Department of Health Research and Development Directorate.
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Protein-polysaccharide conjugate vaccines contain the same polysaccharides from the bacterial surface chemically conjugated to a protein carrier.
“Protein–polysaccharide conjugate vaccines contain the same polysaccharides from the bacterial surface, but in this case they are chemically conjugated to a protein carrier (mostly tetanus toxoid, or diphtheria toxoid or a mutant protein derived from it, known as CRM197)32–34.”
From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [32]
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- Authors
- Andrews, N. J., Waight, P. A., Burbidge, P., Pearce, E., Roalfe, L., Zancolli, M., Slack, M., Ladhani, S. N., Miller, E., & Goldblatt, D.
- Affiliations
- Public Health England (GB)
- University College London (GB)
- Corresponding author
- Goldblatt, David
- Venue
- The Lancet Infectious Diseases
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 14
- Issue
- 9
- Pages
- 839-846
- ISSN
- 1473-3099 (ISSN-L)
- OpenAlex
- W2128013943
- Cited by
- 545
- References
- 24
- Citations by year
- 2026: 28 · 2025: 53 · 2024: 47 · 2023: 37 · 2022: 36 · 2021: 59 · 2020: 52 · 2019: 43 · 2018: 53 · 2017: 43 · 2016: 45 · 2015: 41 · 2014: 7 · 2013: 1
- FWCI
- 34.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Griffith Research Online (submittedVersion)
- Funders
- Public Health England
- Topics
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Keywords
- 13-valent pneumococcal conjugate vaccine, PCV13, PCV7, correlates of protection, invasive pneumococcal disease, serotype-specific IgG, vaccine immunogenicity, infants, serotype 19A, serotype 1
- MeSH terms
- Heptavalent Pneumococcal Conjugate Vaccine, Antibodies, Bacterial, Child, Preschool, Humans, Immunoglobulin G, Infant, Licensure, Serotyping, Cohort Studies, Vaccines, Conjugate, Pneumococcal Vaccines
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