Four PCV Vaccine Schedules Similarly Protect Infants

Larry Hand

September 03, 2013

A trial evaluating 4 immunization schedules with 13-valent pneumococcal vaccine (PCV13) in healthy term infants produced no significant differences in antibody levels after a booster dose for almost all serotypes, according to a study published online September 3 in JAMA.

In secondary analyses, researchers found differences in protection levels between schedules during the primary dosing period, but all children reached equally high IgG levels after the booster dose.

Judith Spijkerman, MD, from the Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, the Netherlands, and colleagues conducted a phase 4 randomized trial involving 400 infants in a general community in the Netherlands between June 2010 and January 2011. Of the 400 infants, 396 (99%) completed the trial.

Researchers randomly assigned the infants to receive PCV13 at 2, 4, and 6 months (2-4-6); at 3 and 5 months (3-5); at 2, 3, and 4 months (2-3-4); or at 2 and 4 months (2-4). All were to receive a booster at 11.5 months. Researchers collected blood samples from the infants 3 times during the year and again at 1 month after the booster dose.

Measuring for IgG geometric mean concentrations, researchers observed no significant differences in IgG among the schedules, except for 8 of 78 comparisons. For instance, the 2-4-6 schedule had higher protection levels than the 2-3-4 schedule for serotypes 18C (10.2 μg/mL [95% confidence interval (CI), 8.2 - 12.7 μg/mL] vs 6.5 μg/mL [95% CI, 5.4 - 7.8 μg/mL] and 23F (10.9 μg/mL [95% CI, 9.0 - 13.3 μg/mL] vs 7.3 μg/mL [95% CI, 5.8 - 9.2 μg/mL], and the 3-5 schedule was superior to 2-4-6 for serotype 1 (11.7 μg/mL [95% CI, 9.6 - 14.3 μg/mL] vs 6.0 μg/mL [95% CI, 4.7 - 7.5 μg/mL]).

"One month after the booster dose, nearly all participants reached the 0.35 μg/mL seroprotection threshold and 71% to 100% reached the 1.00-μg/mL threshold for all serotypes," the researchers write.

Limitations of the study include the inability to exclude interference from coadministrations on immune responses against PCV13, but strengths include the longitudinal randomized trial design and adequate sample size, researchers write.

They conclude, "The choice of PCV schedule will require a balance between the need for early protection and maintaining protection between the primary series and the booster."

In an accompanying editorial, Katherine L. O'Brien, MD, MPH, writes that because pneumococcal disease peaks in high-burden settings during the first year of life, the study's secondary findings are relevant. The study "reassures that PCV products now in use provide a robust immune response across a range of dosing schedules and focuses attention on specific serotypes of concern. … Emphasis on immunogenicity differences should not be separated from the larger context of protection at the individual level, pneumococcal disease epidemiology, vaccine program performance, and ultimately clear measures of disease outcome.

According to the World Health Organization, more than 800,000 children under 5 years old died of pneumococcal disease in 2000.

This research was funded by the Dutch Ministry of Health, with 1400 PCV vaccines provided by Pfizer. Two authors report having received grants, research testimony, or consulting fees from Pfizer and GlaxoSmithKline. One author also reports having served on a pneumococcal vaccine advisory committee for Merck, GlaxoSmithKline, and Aventis-Pasteur. No other authors have disclosed relevant financial relationships.

JAMA. Published online September 3, 2013.


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