Vaccination with the Heptavalent Pneumococcal Conjugate Vaccine Prevenar™ Provides Early Protective Antibody Responses in Children after Allogeneic Stem Cell Transplantation.
Authors: Meisel Roland , Dirksen Uta , Schubert Ralf , Gruhn Bernd , Strauss Gabriele , Duffner Ulrich , Groll Andreas , Beutel Karin , Bluetters-Sawatzki Renate , Holter Wolfgang , Feuchtinger Tobias , Gruettner Hans-Peter , Zielen Stefan , Laws Hans-Juergen , Dilloo Dagmar 
Published: April 2020

Abstract
Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at significant risk for life-threatening infections with Streptococcus pneumoniae especially in the first two years after transplantation. Due to immaturity of the immune system, immunization with conventional pneumococcal polysaccharide vaccine fails to elicit protective immunity in the majority of pediatric HSCT recipients. The heptavalent pneumococcal conjugate vaccine Prevenar™ (PCV7; Wyeth Pharma) provides effective protection from invasive disease in infants, who like aHSCT recipients are unable to respond to polysaccharide vaccines due to immunologic immaturity. Currently there is a dearth of data on the safety and efficacy of PCV7 vaccination in pediatric transplant recipients. Here we report tolerability and profound immunogenicity of PCV7 in children after HSCT and show for the first time that PCV7 provides early protective anti-pneumococcal antibody responses in a homogeneously treated cohort of pediatric HSCT recipients recruited into a prospective, multicenter vaccination trial. 53 children (median age 8,3 (1,416,9) years), who underwent HSCT from related (n=24) or unrelated (n=29) donors were immunized with three doses of PCV7 in monthly intervals starting at 6–9 months after HSCT. PCV7 was administered in combination with a hexavalent vaccine against Tetanus, Diphtheria, Pertussis, Poliovirus, Haemophilus influenzae type B and Hepatitis B (Infanrix hexa™; GlaxoSmithKline Pharma). Serum was obtained at baseline and 4–6 weeks after the 2nd and 3rd vaccine and local and systemic adverse events were recorded for 28 days after each vaccination. Responses, defined as seroconversion to protective serotype-specific antibody concentrations (Ab conc.) of 0,5 mg/ml or &gt;2-fold increase were detected in 41.9% – 86.0% of patients (pts) after the 2nd vaccine and in 58.1% – 90.7% of pts after the 3rd vaccine (n=43). As a result of a highly significant increase in mean geometric Ab conc. (GMCs) (p&lt;0.001) protection to all 7 vaccine serotypes was achieved in 56% and 74% of pts after the 2nd and 3rd application of PCV7 at a median of 10 and 11 months after transplantation, respectively. Even in a small subgroup of pts suffering from chronic GvHD 5/7 pts attained protective Ab conc. to 6/7 serotypes (n=7). Local and systemic tolerability was very good and no vaccine-related severe adverse events were observed. In conclusion, our data show that vaccination with PCV7 elicits highly protective anti-pneumococcal antibody responses in pediatric HSCT recipients within the 1st year following aHSCT. Therefore, PCV7 should be included in routine revaccination programs for pediatric HSCT recipients.