Concentration and high avidity of pneumococcal antibodies persist at least 4 years after immunization with pneumococcal conjugate vaccine in infancy

Abstract

To provide more extensive evidence of long-term effects of vaccination on immunity against Streptococcus pneumoniae, a follow-up study of the Finnish Otitis Media (FinOM) Vaccine Trial was conducted. One of the objectives was to assess the persistence and avidity of pneumococcal antibodies 4 years after pneumococcal vaccination given in infancy. Children with complete follow-up in the FinOM trial up to 24 months of age were invited to a single visit in their fifth year of life. A blood sample was taken from all children for determination of anticapsular antibody concentrations to vaccine serotypes and avidity of antibodies to three serotypes. Children had been vaccinated at 2, 4, 6, and 12 months of age with 7-valent pneumococcal capsular polysaccharide, CRM197 conjugate vaccine (PCV7), or a control vaccine. Serum IgG antibody concentrations to vaccine serotypes remained significantly higher in children who had received PCV7 than in control children for 4 years after the fourth PCV7 dose. Concentrations of antibodies to frequently carried serotypes (6B and 19F) declined less than those of antibodies to a rarely carried serotype (4), suggesting that natural boosting contributed to antibody persistence. Furthermore, antibody avidity was significantly higher in PCV7 than control vaccine recipients. Four doses of PCV7 given in infancy elicit long-lasting antibody responses with high avidity. (This study has been registered at ClinicalTrials.gov under registration no. NCT00378417.).

Figures

Fig 1

Process of sample selection for this study. The sets of sera selected for antibody concentration and avidity determinations, including PS 22F preadsorption, were not the same, and the sets of sera for different serotypes were not the same in these determinations.

Fig 2

Kinetics of serum pneumococcal IgG antibodies during the first 5 years of life in children immunized with PCV7 or control vaccine at the ages of 2, 4, 6, and 12 months; n (2 to 24 months) = 52 to 58; n (5 years) = 341 to 382.

Fig 3

Reverse cumulative distribution curves of the serum pneumococcal IgG antibody concentrations in the fifth year of life of children who received four doses of PCV7 or control vaccine in infancy. The vertical lines denote the IgG reference concentrations of 0.35, 1.0, and 5.0 μg/ml.

Fig 4

Effect of PS 22F preadsorption on IgG antibody concentration (results are GMC, in μg/ml, with 95% CI) kinetics in the PCV7 (n = 25 to 29) and control (n = 20 to 29) groups between 13 months and 5 years of age for serotypes 4, 6B, and 19F.

Fig 5

Pneumococcal IgG antibody avidity (results are GMAI, with 95% CI) kinetics between 13 months and 5 years (60 months) of age in the PCV7 (n = 30) and control (n = 11 for serotype 4, n = 30 for 6B and 19F) vaccine groups. The vaccines were administered at 2, 4, 6, and 12 months of age.