Abstract
Purpose
Hematopoietic cell transplantation (HCT) recipients are vulnerable to invasive infection by Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). This study was performed to evaluate immune responses after Hib and Sp vaccination in Korean pediatric HCT recipients. Methods: Patients were prospectively enrolled at Samsung Medical Center during 2009–2011. ELISA tests to detect anti- PRP IgG antibody and antibodies to Sp serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were performed at the Center for Vaccine Evaluation and Study, Ewha Medical Research Institute. Results: Ten patients (two allogeneic, eight autologous recipients) with median age 5.4 years (range 2.7–12.2 years) were enrolled. Before Hib vaccination, 60% of patients' anti-PRP IgG titers were below 0.15 μ g/mL. After vaccination, 100% of patients' anti-PRP IgG titers increased above 0.15 μ g/mL (cut-off value for detection) and 1.0 μ g/mL (cut-off value for seroprotection). For pneumococcus, in 2–5 year-old patients, pre-vaccination geometric mean concentrations (GMCs) of IgG for six serotypes (4, 6B, 9V, 14, 18C, and 23F) were below 0.35 μ g/mL and at 5 months post-vaccination GMCs of IgG for all seven serotypes increased to above 0.35 μ g/mL. In patients older than 5 years, pre-vaccination GMCs of IgG for four serotypes (4, 9V, 14, and 23F) were below 0.35 μ g/mL and at 3 months post-vaccination GMCs of IgG for all seven serotypes increased to above 0.35 μ g/mL. Conclusion: Most HCT recipients had low or no protective antibodies to Hib and Sp before vaccination, but showed good immune responses to protective levels after vaccination.
References
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Fig. 1.
Lymphocyte proliferation test of enrolled patients before vaccination. Patients' lymphocyte proliferation activity was measured by stimulating lymphocytes in vitro with PHA and ConA, and SI was calculated by comparing the value to normal controls. Each line shows changes in SI values according to the concen-tration of PHA and ConA. Black dotted lines represent the median SI values of lymphocytes from immunocompetent normal control individuals. PHA, phytohe-magglutinin; ConA, concanavalin A; SI, stimulation index.
![kjpid-21-81f1.tif](/upload/SynapseXML/0153kjpid/thumb/kjpid-21-81f1.gif)
Fig. 2.
Anti-PRP IgG concentrations after Hib vaccination. Hib vaccination was performed at months 0, 2, and 12, and blood draws for serological tests were performed at months 0, 3, and 13. The third Hib vaccination was not performed in patient 6 and 7.
![kjpid-21-81f2.tif](/upload/SynapseXML/0153kjpid/thumb/kjpid-21-81f2.gif)
Fig. 3.
Antibody response for S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in group I (A) and group II (B) A. In group I, antibodies were measured after two doses of PCV7 and one dose of PPSV 23 in patients 2–5 years of age. Patients were vaccinated with PCV7 at months 0 and 2, and with PPSV23 at month 4. Blood was drawn for serological testing at months 0, 3, 5 and 13. B. In group II, antibodies were measured after one dose of PPSV23 at month 0 and blood was drawn for serological tests at months 0, 1, 3, and 13. GMC, geometric concentration; PCV7, pneumococcal conjugate vaccine 7-valent; PPSV23, pneumococcal polysaccharide vaccine 23-valent; Pre, prevaccination.
![kjpid-21-81f3.tif](/upload/SynapseXML/0153kjpid/thumb/kjpid-21-81f3.gif)
Table 1.
Schedule for Vaccination and Serum Collection
Abbreviations: Hib, Haemophilus influenzae type b; PCV7, 7-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneu-mococcal polysaccharide vaccine; HepB, hepatitis B vaccine; DTaP, diphteria-tetanus-acellular pertussis vaccine; Td, tetanus- diphteria vaccine; IPV, inactivated polio vaccine; HepA, hepatitis A vaccine; MMR, measles-mumps-rubella vaccine was given to patients when at least 2 years have passed after last HCT and the patient was off from immunosuppressive agent or intravenous immunoglobulin for at least one year more.
Table 2.
Patient Characteristics
Table 3.
Lymphocyte Subsets before Vaccination
Table 4.
Immunoglobulin Values before Vaccination
Table 5.
Reported Adverse Events of Grade III or more after Vaccination
Group I (n=16)∗ | Group II (n=16)† | Total (n=32) | ||||
---|---|---|---|---|---|---|
Case | % | Case | % | Case | % | |
Redness | 0 | 0.0 | 1 | 6.25 | 1 | 3.1 |
Pain | 0 | 0.0 | 1 | 6.25 | 1 | 3.1 |
Swelling | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Induration | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Fever (≥39.5℃) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Lethargy | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Allergic reaction | 0 | 0.0 | 1 | 6.25 | 1 | 3.1 |
Rash | 0 | 0.0 | 1 | 6.25 | 1 | 3.1 |
Muscle pain | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Joint pain | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Summary | 0 | 0.0 | 4 | 25.0 | 4 | 12.5 |
Table 6.
Anti-PRP IgG Concentration after Haemophilus influenzae Type b Vaccination
Patient ID | Anti-PRP IgG concentration (mg/mL) | ||
---|---|---|---|
Pre-vaccination (month 0) | One month after 2 nd dose (month 3) | One month after 3 rd dose (month 13) | |
1 | 0.08 | 81.57 | 151.29 |
2 | 0.08 | 0.20 | 36.74 |
3 | 0.08 | 112.84 | 310.47 |
4 | 2.85 | 33.49 | 206.37 |
5 | 0.08 | 144.66 | 715.35 |
6 | 0.08 | 19.42 | ND |
7 | 1.40 | 74.00 | ND |
8 | 0.08 | 3.55 | 54.84 |
9 | 1.02 | 3.27 | 33.70 |
10 | 3.69 | 4.35 | 7.99 |
GMC (95% CI) | 0.29∗, † (0.09–0.96) | 15.17∗ † (3.37–68.43) | 88.50† (26.38–296.80) |
Table 7.
Antibody Response after Two Doses of 7-valent Pneumococcal Conjugate Vaccine and One Dose of 23-valent Pneumococcal Polysaccharide Vaccine in Patients Aged 2–5 Years (Group I)
Table 8.
Antibody Response after One Dose of 23-valent Pneumococcal Polysaccharide Vaccine in Patients Aged >5 Years (Group II)
Serotype | GMC of IgG (mg/mL) (95% CI) | |||
---|---|---|---|---|
Pre-vaccination (month 0) n=6 | 1 month after PPSV 23(month 1) n=2 | 3 months after PPSV 23 (month 3) n=6 | 13 months after PPSV 23 (month 13) n=4 | |
4 | 0.09 (0.04–0.21) | 0.61∗∗ | 0.63 (0.17–2.36) | 0.23 (0.03–2.04) |
6B | 0.59 (0.13–2.74) | 0.53 (0.001–234.00) | 2.17 (0.25–19.10) | 0.80 (0.09–7.41) |
9V | 0.16 (0.05–0.47) | 0.49 (0.01–36.66) | 0.56 (0.14–2.25) | 0.31 (0.10–0.96) |
14 | 0.27 (0.08–0.97) | 0.51 (0.35–0.74) | 0.74 (0.12–4.42) | 0.68 (0.02–28.17) |
18C | 0.48 (0.11–2.16) | 0.22 (0.12–0.39) | 0.94 (0.15–6.08) | 0.43 (0.04–4.42) |
19F | 1.07 (0.32–3.64) | 1.48 (0.03–78.88) | 2.47 (0.68–8.95) | 1.60 (0.23–10.97) |
23F | 0.24 (0.08–0.68) | 0.12† | 0.37 (0.03–4.22) | 0.15 (0.03–0.95) |