Home > DARE Reviews > Immunogenicity of pneumococcal conjugate...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Immunogenicity of pneumococcal conjugate vaccines in infants after two or three primary vaccinations: a systematic review and meta-analysis

S Ruckinger, R Dagan, L Albers, K Schonberger, and R von Kries.

Review published: 2011.

CRD summary

Most children were protected by two primary immunisations with PCV vaccine, apart from serotypes 6B and 23F in which the potential benefit of three primary vaccinations was considerable. The authors' conclusions reflect the evidence presented but the unknown quality of the included studies and differences between the included studies make the reliability of the conclusions unclear.

Authors' objectives

To evaluate the evidence on immunogenicity of pneumococcal conjugate vaccines (PCV) in infants comparing two and three primary immunisations before a booster dose is given.

Searching

MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 1999 to 2011. Search terms were reported. Studies reported in English, French and German were considered. Drug manufacturers were contacted for any relevant additional study material.

Study selection

The included studies had to report the proportion of children with ELISA antibody levels of at least 35μg/mL after primary infant immunisation.

Eligible studies were RCTs that compared two with three primary immunisations (type B) and single-arm trials (three primary immunisations) and compared antibody levels after two and after three immunisations in the same patients (type A). Studies of children immunised after six months were excluded. Three pneumococcal conjugate vaccines (PCV7, PCV10 and PCV13) licensed in Europe and USA were eligible for inclusion in this study. The difference between the proportion of participants with antibody levels of at least 0.35μg/mL after two and three doses of PCV was chosen as an endpoint.

Studies were conducted in Germany, Poland, Spain, Denmark, Norway, Slovakia, Sweden, Fiji, Korea, Israel and The Gambia. RCTs used a vaccination schedule of two, four and six months. Schedules in single-arm trials varied. Antibody levels were evaluated one month after each vaccination for all studies.

The authors did not state how many reviewers were involved in study selection.

Assessment of study quality

The authors did not report that they assessed validity.

Data extraction

Data were extracted on the proportions of children who achieved the specified antibody level for each serotype after two and three doses of the vaccine.

Two reviewers independently extracted the data. Any disagreements were resolved by discussion to reach consensus.

Methods of synthesis

Pooled differences in the proportion of children with antibody levels of at least 0.35 μg/ml were calculated, with 95% confidence intervals (CIs). DerSimonian and Laird random-effects model meta-analysis was used. Statistical heterogeneity was assessed using the Ι² statistic.

Results of the review

For most serotypes, well over 90% of children had protective antibody levels after three doses.

Type A (four studies): One study used PCV7, one study used PCV7 and PCV10 and two studies used PCV13. Substantial heterogeneity (Ι²=97.9%) between serotypes and studies was observed. The largest differences between two and three doses was observed for serotypes 6B (-49.4%, 95% CI -66.0% to -32.9%), 23F (-26.9%, 95% CI -37.2% to -16.6%) and 6A (-15.4%. 95% CI -20.6% to -10.3%). For all other serotypes the difference was less than 10%.

Type B (four RCTs): Three studies used PCV7 and one study used PCV10. There was a substantial heterogeneity (Ι²=90.4%) between serotypes and studies. The largest difference between groups of children achieving protective antibody levels was observed for serotypes 6B (-20.3%. 95% CI -36.1% to -4.6%) and 23F (-19.7%, 95%CI -32.8% to -6.5%). For all other serotypes, the difference was less than 10%.

Antibody levels at 12 months were reported for two studies.

Authors' conclusions

Most children were protected by two primary immunisations with PCV vaccine except for serotypes 6B and 23F in which the potential benefit of three primary vaccinations was considerable. For all other serotypes, the difference between two and three primary immunisations was less than 10%.

CRD commentary

The review addressed a clear question and was supported by appropriate inclusion criteria. Several relevant data sources were searched. The restriction to studies in English, German and French meant that language bias was possible. Two reviewers extracted data. The authors did not report how many reviewers performed study selection so some studies may have been missed.

The authors did not report any assessment of study quality so it was difficult to assess the reliability of the evidence included in the review. Use of a random-effects model was appropriate considering the substantial statistical heterogeneity between both studies and serotypes. The authors attempted to explain possible sources of the heterogeneity.

The authors' conclusions reflect the evidence presented but the unknown quality of the included studies, high heterogeneity and possible language bias make the reliability of the conclusions unclear.

Implications of the review for practice and research

Practice: The higher cost of three primary immunisations and one booster meant that a reduction to two primary immunisations and one booster dose might be considered in countries where serotypes 6B and 23F were relevant.

The authors did not state any implications for further research.

Funding

Not stated.

Bibliographic details

Ruckinger S, Dagan R, Albers L, Schonberger K, von Kries R. Immunogenicity of pneumococcal conjugate vaccines in infants after two or three primary vaccinations: a systematic review and meta-analysis. Vaccine 2011; 29(52): 9600-9606. [PubMed: 21933696]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antibodies, Bacterial /blood; Health Services Research; Humans; Immunization, Secondary /methods; Infant; Pneumococcal Infections /immunology /prevention & control; Pneumococcal Vaccines /administration & dosage /immunology; Vaccination /methods; Vaccines, Conjugate /administration & dosage /immunology

AccessionNumber

12012000054

Database entry date

23/10/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 21933696

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...