Serum Opsonic Activity in Infants with Sickle-Cell Disease Immunized with Pneumococcal Polysaccharide Protein Conjugate Vaccine

Abstract

Pneumococcal infections are an important cause of morbidity and mortality in children with sickle-cell disease (SCD). Pneumococcal conjugate vaccines (PCVs) are immunogenic in healthy infants <2 years of age but have not been evaluated in young children with SCD. Infants with SCD were immunized with a 7-valent PCV (Wyeth-Lederle Vaccines & Pediatrics) at 2, 4, and 6 months of age. A booster dose of 23-valent pneumococcal polysaccharide vaccine (PPV; Pnu-Immune) was administered at 24 months of age. Antipneumococcal type 6B and 14 serum opsonic activity was measured to assess the biologic function of the antibody. Following the administration of three doses of PCV, opsonic activity against serotype 6B increased from 4.8% at 2 months to 33.5% at 7 months, with a subsequent decline to 8.1% at 12 months and 7.5% at 24 months and with an increase to 30.7% at 25 months after administration of a booster dose of PPV. Similar trends were seen with serotype 14 (opsonic activities were 9.4% at 2 months, 24.9% at 7 months, 16.5% at 12 months, and 12.6% at 24 months, and the opsonic activity was 27.3% 1 month after the administration of PPV). Serum opsonic activity correlated with antibody levels for both serotypes. PCV induces serum opsonic activity in infants with SCD. Antipneumococcal serum opsonic activity correlates with antibody levels.Patients with sickle-cell disease (SCD) have an increased susceptibility to blood-borne Streptococcus pneumoniae infections such as sepsis and meningitis (1,26,38). In fact, their risk for invasive pneumococcal infection has been estimated to be as high as 300 to 600 times that of children of the same age without SCD (1, 38).A variety of strategies have been used to protect children with SCD against pneumococcal infection. One such strategy has been to use penicillin prophylaxis (10). However, inconsistent compliance and the emergence of bacterial resistance may limit the protective effect of antibiotic prophylaxis (6, 33). Another strategy has been immunization with the currently available 23-valent capsular polysaccharide pneumococcal vaccine. However, that vaccine is not immunogenic in children younger than 2 years of age, the very age at which there is the highest incidence of pneumococcal sepsis (1,6,20).A new pneumococcal polysaccharide protein conjugate vaccine has been shown to be immunogenic and effective in preventing invasive pneumococcal disease in healthy infants and children younger than 2 years of age (5,25). This vaccine has the potential to be of particular benefit to infants and young children with SCD. Our previous studies demonstrated that this conjugate vaccine is immunogenic in infants younger than 1 year of age with SCD (19). We performed the current studies in order to determine whether the anticapsular antibody induced by this vaccine possesses opsonic activity, perhaps a better correlate of biologic activity than antibody level measured by enzyme-linked immunosorbent assay (ELISA). MATERIALS AND METHODSImmunization protocol and serum samples. The infants in this...

Sickle Cell Trait, Hemoglobin C Trait, and Invasive Pneumococcal Disease

“…3,6,9,10 Although the exact mechanism for this protection is not known, serum-opsonization activity in children with sickle cell disease increased after PCV7 vaccination, and is correlated with antibody levels. 11 In contrast, sickle cell trait has been generally considered benign and not associated with increased risk of bacterial infections in childhood.…”

13‐valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6‐17 years of age with sickle cell disease previously vaccinated with 23‐valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study

“…In our study population, altered immune function associated with functional or anatomic asplenia cannot be ruled out as a contributor to the reduced immune responses observed. However, infants with SCD are generally able to mount PCV immune responses measured as IgG binding and OPA functional antibody responses that are as robust as those of healthy infants .…”

Nasopharyngeal carriage rate of Streptococcus pneumoniae in children with sickle cell disease before and after the introduction of heptavalent pneumococcal conjugate vaccine

“…Non-compliance with antibiotic prophylaxis, emergence of penicillin resistant pneumococci and lack of immunological memory associated with PPV-23 vaccination are among proposed causes of failure [4][5][6][7][8]. Therefore, development of more highly immunogenic vaccines, e.g., by linking pneumococcal polysaccharides or parts of them to protein carriers has been achieved [9][10][11].…”