Purpose of the Study:
The pneumococcal polysaccharide-protein conjugate vaccine (PCV) is a part of the primary vaccination series recommended by the World Health Organization (WHO) as well as the Centers for Disease Control and Prevention (CDC). The purpose of this study was to examine the protective antibody response at 7 and 13 months to PCV by following the primary vaccination series recommended by the WHO, using the 3 + 0 schedule (PCV at 6 weeks, 3–4 months, and 4–6 months of age).
Patients were gathered from a previous patient population that was a part of the Melbourne Infant Study: BCG for Allergy and Infection Reduction that was looking at BCG immunization at birth and the protective nature against allergy, childhood infection, and asthma from whom blood samples were collected at 7 and/or 13 months of age. All of these infants were in Melbourne, Australia, and were a part of the Australian National Immunization program from 2013 to 2016. Inclusion criteria were infants born at >32 weeks’ gestation, birth weight >1500 g, mother who was not HIV positive, absence of symptoms or signs of illness, and no known contact with tuberculosis. Twins of the participants were excluded from the study because they were not considered independent.
Samples were examined for pneumococcal-specific antibody concentration to all 13 antigens included in the PCV 13 by using a fluorescent bead–based multiplex immune assay. An antibody concentration of 0.35 µg/mL is conventionally considered the threshold protection level for invasive pneumococcal disease, 0.5 µg/mL is the level for mucosal pneumococcal disease protection, and 2 μg/mL is the level for crossprotection between serotypes. Samples obtained at 7 and/or 13 months of age were assayed to determine the geometric mean concentrations (GMCs) for each vaccine antibody level, and the 95% confidence intervals were determined at both time points.
Ninety-one infants were included at 7 months, and 311 infants were included at 13 months. There were no significant demographic differences between groups, with even distributions of sex, gestational age, birth weight, delivery mode, and age of immunization. At 7 months of age, the GMCs varied between 0.52 μg/mL and 11.53 μg/mL. Seroprotection rates using 0.35 µg/mL for invasive pneumococcal disease varied between 69% and 100%. The lowest protection was seen for serotypes 4 and 6B. The seroprotection rate for the other 11 subtypes was >90%. Using the 0.5 µg/mL threshold for seroprotection, the rates decreased to between 53% and 100%, with most serotypes having 83% to 89% seroprotection and the lowest rates being in serotypes 4 (53%) and 6B (85%). At 13 months of age, there was a notable decrease in the protective antibodies for all serotypes measured in the blood samples, with GMCs varying between 0.22 μg/mL and 3.09 μg/mL. Seroprotection rates were <90% for most serotypes (10 out of 13) using the 0.35 µg/mL threshold, with the lowest rates for serotypes 4 (23%), 19A (50%), 23F (61%), and 6B (64%). Using a threshold of 0.5 µg/mL, the rate of seroprotection was between 13% and 98%, with 8 serotypes having <80% seroprotection and <60% protective level of antibodies in 6 serotypes. The lowest were serotypes 4 (13%), 19A (37%), 3 (47%), 23F (50%), and 6B (52%).
With the recommended WHO vaccine schedule at 6 weeks, 3 to 4 months, and 5 to 6 months for PCV 13, pneumococcal antibody titers to the different specific serotypes at 13 months (which is 7 months after the last immunization) are lower than would be considered seroprotective. These infants should be considered at risk for these invasive pneumococcal diseases and thus warrant additional administrations of the vaccine.
Streptococcus pneumoniae remains an important organism causing significant morbidity and mortality worldwide. PCV 13 can induce seroprotective antibodies to protect children that are at high risk of developing pneumococcal diseases. This article indicates there is a progressive waning of antibodies for pneumococcus, which could place children at risk for invasive pneumococcal disease. The current WHO recommendations are based on either a 3 + 0 schedule with vaccines at 6 weeks, 3 to 4 months, and 4 to 6 months of age or a 2 + 1 schedule with 2 doses before 6 months as well as a booster at 9 to 15 months. This differs from the CDC 2019 recommendation, which is the 3 + 1 schedule with doses at 2, 4, and 6 months and a booster at 12 to 15 months of PCV 13. Although the timing of the first 3 doses is similar between WHO and CDC, the additional booster seems to be key for lasting protection. The novelty of this article is that it demonstrated a waning phenomenon of pneumococcal protection in infants who were initially protected on the basis of testing obtained 1 month after immunization, but 7 months after the third vaccine, these antibody levels did not persist. This article can be used to help arm pediatricians with science-driven data that can be used in discussions with parents about the reasoning behind the vaccination schedule as it is currently designed. The researchers also suggest follow-up titers when measuring pneumococcal immune responses >6 months from the last vaccine to measure the persistence of protection.