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

Abstract

The European Group for Blood and Marrow Transplantation has recently run a prospective, randomized trial comparing an early (3 months) vs a late (9 months) immunization program after allo-SCT with three doses of the conjugate 7-valent pneumococcal vaccine. This trial has shown that the response rate assessed 1 month after the third dose of conjugate vaccine was not inferior after an early vaccination vs a late vaccination. Part of the responder cohort of these patients (n ¼ 28) were chosen to assess the functionality of the anti-pneumococcal antibodies through an opsonophagocytic assay, 1 month after the third dose of conjugate vaccine. We have assessed the relationship between IgG titers measured by the pneumococcal ELISA and functional titers measured by opsonophagocytic assay of anti-pneumococcal antibodies. We found a significant correlation between titers for both assays, and conclude that the response to PCV7 after SCT induces functional antibodies. Bone Marrow Transplantation (2010Transplantation ( ) 45, 1423Transplantation ( -1426 doi:10.1038/bmt.2009; published online 21 December 2009 Keywords: conjugate pneumococcal vaccine; opsonocytophagocytic activity; allo-SCT IntroductionAllogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk of Streptococcus pneumoniae invasive infection, around 20 times more than the normal population. 1 This event can be prevented by immunoglobulins or by active immunization. Both the polysaccharide 23-valent vaccine (PPV23) and the 7-valent conjugate vaccine (PCV7) have been assessed after HSCT. The immune response to the PPV23 is suboptimal during the first year after transplant, and even later in the case of chronic GVHD or immunosuppressive drugs. 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. 7 However, although antipolysaccharide-specific Ab levels measured by ELISA are the main parameter used to measure the vaccine-induced protection, they may not fully reflect the functional ability of the antibodies to kill S. pneumoniae in vivo, especially in immunocompromised patients. As opsonocytophagotytosis is essential in the host defense against S. pneumoniae, 8 the use of an in vitro opsonophagocytic assay (OPA) is recommended as a secondary end point in pneumococcal vaccine trials. 9 One of the secondary end points of the IDWP01 trial was to assess the OPA of the sera collected from randomly chose...

Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia

“…In contrast, our results differ from those of a study of allogeneic stem cell-transplanted patients with hematological malignancies, where significant correlations between antipneumococcal IgG and OPA titers were found for all seven investigated pneumococcal serotypes (25). Of note is that the patients in that study (mean age, 37 years) were younger than ours and had different hematological diagnoses and thus may have been able to mount better IgG responses.…”

How I vaccinate blood and marrow transplant recipients

“…Consensus guidelines recommend initiating vaccinations at 3 to 6 months after BMT noting that this lacks prospective validation. [1][2][3][4][5] Given the variable tempo of IR (see sFAQ 1), particularly in patients transplanted for primary immunodeficiency diseases (see FAQ 4), the negative impact of moderate to severe GVHD on IR, and potential use of in vivo T-or B-cell depleting therapies, we prefer to select candidates for "early vaccination" at 6 months based on favorable responses to a 6-question algorithm ( Figure 2). Any unfavorable response triggers vaccine deferral (except for flu shots) until at least 1 year posttransplant.…”

“…Sound OK?"). If a participatory approach is preferred, commit to pursuing any refusals, concerns, or questions knowing that approximately half of the initially vaccine-resistant parents and a quarter of vaccine-hesitant parents will change their mind (see sFAQ [4][5][6].…”

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.…”