Format

Send to

Choose Destination
Lancet Infect Dis. 2014 Sep;14(9):839-46. doi: 10.1016/S1473-3099(14)70822-9. Epub 2014 Jul 17.

Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study.

Author information

1
Statistics, Modelling, and Economics Department, Health Protection Services, Public Health England, London, UK.
2
Immunisation, Hepatitis, and Blood Safety Department, Health Protection Services, Public Health England, London, UK.
3
Immunobiology Section, UCL Institute of Child Health, London, UK.
4
Respiratory and Vaccine Preventable Bacteria Reference Unit, Microbiology Services, Public Health England, London, UK.
5
Immunobiology Section, UCL Institute of Child Health, London, UK. Electronic address: d.goldblatt@ucl.ac.uk.

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.

PMID:
25042756
DOI:
10.1016/S1473-3099(14)70822-9
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center