Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation

Abstract

Following allogeneic hematopoietic stem cell transplantation (alloHSCT), children are at risk of life-threatening pneumococcal infections. Whereas vaccination with polysaccharide vaccines fails to elicit protective immunity in most alloHSC transplant recipients, pneumococcal conjugate vaccines may effectively prevent invasive disease by eliciting T-cell-dependent antibody responses. Here, we report safety and immunogenicity in 53 children immunized with a regimen of 3 consecutive doses of a heptavalent pneumococcal conjugate vaccine (7vPCV) in monthly intervals starting 6 to 9 months after alloHSCT. Immunization was well tolerated with no vaccine-related serious adverse events. Serologic IntroductionPatients following allogeneic hematopoietic stem cell transplantation (alloHSCT) are at significant risk of life-threatening infections despite leukocyte engraftment. 1,2 This is based on the loss of protective immunity to vaccine-preventable diseases and the relative immaturity of the emerging immune system. [3][4][5][6][7][8][9] In this setting, infections with encapsulated bacteria, particularly pneumococci, are associated with significant rates of morbidity and mortality. 10,11 Epidemiologic studies have shown a cumulative incidence of invasive pneumococcal disease between 1% and 10% with a median onset at 1 year following transplantation. 12,13 Therefore, effective prevention, including chemoprophylaxis and active immunization, is warranted. This is particularly true for children who on reintegration into day care and school become highly exposed to pathogens. Current guidelines of the Centers for Disease Control and Prevention (CDC) and the European Blood and Marrow Transplantation group (EBMT) generally recommend vaccination of all alloHSC transplant recipients with the standard 23-valent pneumococcal polysaccharide vaccine starting at 12 months after transplantation. 14,15 Because of immaturity of the immune system, however, vaccination with polysaccharide vaccines fails to elicit protective immunity in the majority of pediatric alloHSC transplant recipients, with response rates ranging from 20% to 30% in the first to 50% in the second year after alloHSCT. 16,17 In contrast, in the heptavalent pneumococcal conjugate vaccine (7vPCV), serotypespecific polysaccharides are conjugated to an immunogenic protein carrier and hence elicit T-cell-dependent antibody responses. 7vPCV contains the 7 most prevalent pneumococcal serotypes and The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From provides effective protection against invasive disease in infants and young children who, like alloHSC transplant recipients, only weakly respond to polysaccharide vaccines as a result of immunologic immaturity. [18][19][20] Currently,...

Long-term persistence of the immune response to antipneumococcal vaccines after Allo-SCT: 10-year follow-up of the EBMT-IDWP01 trial

“…6,7 Furthermore, a dose of 23-valent polysaccharide vaccine (PPV23) given at 12 months after transplant pneumococcal not only induce an immune response to the PCV7 serotypes in 42% of the previously non-responder patients but also extends the serotype coverage to the PPV23-specific serotypes in 80% of them. 6 On the basis of this study [6][7][8] and others 9,10 showing the immunogenicity of the PCV7 during the first year of transplant, the current international guidelines recommend three doses of PCV13 -which substituted to PCV7 in 2010 on the basis of pediatric studies 11 -at 1-month interval, to be started from 3 to 6 months after transplant, followed at 12 months after transplant by either a dose of PPV23 if the patient has no chronic GVHD or an additional dose of PCV13 in case of chronic GVHD. 4,5 In the IDWP01 trial, we followed the patients until 24 months after transplant, which is, to our knowledge, the latest date so far assessed in a controlled trial for durability of the antipneumococcal immune response in HSCT recipients.…”

Pretransplant vaccinations in allogeneic stem cell transplantation donors and recipients: an often-missed opportunity for immunoprotection?

“…[9][10][11][12] The median onset of invasive diseases occur 1 year post HSCT, although infections occur also early after HSCT. [10][11][12][13] Vaccination before transplant in both donors and recipients has shown to influence Ab responses post transplant. 9,14,15 In the United States, there are currently two pneumococcal vaccinations available that include the PCV13 (pneumococcal conjugate vaccine) and the PPV23 (pneumococcal polysaccharide vaccine).…”

Relationship between IgG titers and opsonocytophagocytic activity of anti-pneumococcal antibodies after immunization with the 7-valent conjugate vaccine in allogeneic stem cell transplant

“…2 The PCV7 is more immunogenic than the polysaccharide vaccine, both in infants 3 and in HSCT recipients 4 and has been evaluated in adults 5 and pediatric transplant recipients. 6 Because pneumococcal infection may occur before 6 months, 1 the EBMT has run a prospective trial (IDWP01) to compare the immune response after an early vs a latestarting at 3 or at 9 months after transplant-immunization with three doses of PCV7. We showed that the pneumococcal IgG ELISA response rate 1 month after three PCV7 doses was not lower in the early group (45/57; 79%) than in the late group (47/57; 82%): the 90% CI for the difference was À3.5% (À15.6, 8.6), which was well above the À20% non-inferiority criterion.…”