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Published on: February 15, 2013
Systematic review of the effect of pneumococcal conjugate vaccine dosing schedules on immunogenicity
Maria Deloria Knoll1, Daniel E Park, T Scott Johnson
1From the *International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; †Biostatistics Consulting, Chicago, IL; ‡Respiratory Diseases Branch, Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; §Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA; ¶Institute of Child Health, University College London, London, United Kingdom.
Insights
Optimal pneumococcal conjugate vaccine (PCV) schedules for infants remain debated. A systematic review found that a third PCV dose in the second year of life yields higher antibody levels, but early protection may be lower than with a three-dose primary series.
Area of Science:
- Immunology
- Vaccinology
- Pediatrics
Background:
- Pneumococcal conjugate vaccines (PCV) offer significant benefits, yet optimal infant dosing schedules require further clarification.
- Infant immunogenicity studies are crucial for determining effective vaccination strategies.
Purpose of the Study:
- To systematically review PCV immunogenicity data and assess the impact of different dosing schedules on infant antibody responses.
- To compare antibody concentrations and serotype-specific protection across various PCV schedules.
Main Methods:
- A systematic literature review of PCV immunogenicity studies published between 1994 and 2011 was conducted.
- Included studies evaluated at least two doses of 7-valent or higher PCV in non-high-risk infants up to 6 months of age.
- Geometric mean concentrations (GMC) and proportions of subjects achieving protective antibody levels were analyzed using random effects linear regression.
Main Results:
- Sixty-one studies encompassing 2+0, 3+0, 2+1, and 3+1 PCV schedules were evaluated.
- Three-dose primary schedules (3+0) resulted in higher GMCs than two-dose schedules (2+0) for most serotypes.
- Administering the third dose in the second year of life (2+1) significantly increased GMCs compared to the 3+0 schedule.
Conclusions:
- While a third PCV dose in the second year (2+1 schedule) enhances antibody response, the interval after a two-dose primary series may offer less protection.
- The theoretical benefits of delayed third doses, including broader serotype coverage and herd immunity, require further practical evaluation.
- Optimizing PCV schedules is essential for maximizing infant protection against pneumococcal disease.
Background:
Despite the breadth of studies demonstrating benefits of pneumococcal conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing schedule in infants.
Methods:
We conducted a systematic literature review of PCV immunogenicity published from 1994 to 2010 (supplemented post hoc with studies from 2011). Studies included for analysis evaluated ≥2 doses of 7-valent or higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk infants ≤6 months of age. Impact of PCV schedule on geometric mean antibody concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at various time points; the GMC 1 month postdose 3 (for various dosing regimens) for serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects linear regression, adjusted for product, acellular diphtheria-tetanus-pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory method, age at first dose and geographic region.
Results:
From 61 studies, we evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a booster dose, 11 "2+1" (2 primary plus booster) and 42 "3+1" schedules. The GMC after the primary series was higher following 3-dose schedules compared with 2-dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs were generally similar regardless of whether 2 or 3 primary doses were given. GMCs were significantly higher for all serotypes when dose 3 was administered in the second year (2+1) compared with ≤6 months of age (3+0).
Conclusions:
While giving the third dose in the second year of life produces a higher antibody response than when given as part of the primary series in the first 6 months, the lower GMC between the 2-dose primary series and booster may result in less disease protection for infants in that interval than those who completed the 3-dose primary series. Theoretical advantages of higher antibodies induced by giving the third dose in the second year of life, such as increased protection against serotype 1 disease, longer duration of protection or more rapid induction of herd effects, need to be evaluated in practice.
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