Opsonophagocytic activity against Streptococcus pneumoniae type 19F in allogeneic BMT recipients before and after vaccination with pneumococcal polysaccharide vaccine

Abstract

Summary:Opsonophagocytic activity (OPA) of pneumococcal polysaccharide (Pnc PS) antibodies in vitro, a measure of antibody functional activity, usually correlates with specific IgG antibody concentrations measured by an EIA method. In order to investigate the functional activity of specific Pnc PS antibodies, we determined IgG antibodies to Pnc PS type 19F by an EIA method and OPA against Pnc type 19F by a killing assay in a randomized study, where 23 adult allogeneic BMT recipients were vaccinated with Pnc PS vaccine at 8 months (early group) and 21 recipients at 20 months (late group) after transplantation. Serum samples drawn before BMT, before vaccination, and at 1 and 16 months after vaccination were available from 27, 35, 34 and 30 patients, respectively. The geometric mean antiPnc 19F concentrations were 4.3, 1.3, 1.6 and 1.3 g/ml in the early group and 3.8, 0.9, 0.6 and 0.6 g/ml in the late group before transplantation, before vaccination, and at 1 and 16 months after vaccination, respectively. OPA (titre у8) was found in 10/27, 5/35, 5/34 and 6/30 patients before BMT, before vaccination, and at 1 and 16 months after vaccination, respectively. The specific IgG antibody concentration and OPA correlated with each other before BMT, and in the early group patients before and at 1 month after vaccination. The results demonstrate that after Pnc PS vaccination allogeneic BMT recipients have antibodies with low functional activity to a Pnc PS antigen associated with low specific IgG responses. There is a need to study new Pnc conjugate vaccines in multi-dose schedules for their capacity to elicit higher specific antibody concentrations with high OPA in BMT recipients. Bone Marrow Transplantation (2001) 27, 207-211. Keywords: opsonophagocytic activity; BMT recipients; pneumococcal antibodies Streptococcus pneumoniae (Pnc) is the main cause of bacterial infections in allogeneic BMT recipients surviving Ͼ3

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

“…Antibodies to Spn capsular polysaccharides [43,44] and to pneumococcal surface protein A (PspA) [42] mediate opsonophagocytic killing of Spn. This study and our previous study [29] have shown that vaccination with trivalent PPrV elicits high sera and lung mucosal IgG responses to PhtD, PcpA and PlyD1 in mice.…”

“…Antibody-mediated opsonization and phagocytosis is an important defense mechanism against Spn [42][43][44]. Antibodies to Spn capsular polysaccharides [43,44] and to pneumococcal surface protein A (PspA) [42] mediate opsonophagocytic killing of Spn.…”

Assessment of Antibody Response Elicited by a 7-valent Pneumococcal Conjugate Vaccine in Pediatric Human Immunodeficiency Virus Infection

“…Clinical and mouse protection data for the selected serotypes for which this assay works indicate that the opsonophagocytosis assay provides the best basis for protection (12,24). Measuring OPA titers has revealed low functional activity of conjugate vaccine-induced antibodies in bone marrow transplant recipients (18) and different responses to conjugate and plain polysaccharide vaccines in children and adults with sickle cell disease (25).…”

Pneumococcal vaccination in adults: recent evidence from clinical trials and observational studies

“…However, the ELISA assay does not always predict serotype protection, especially in older adults and immunosuppressed populations [24,25]. This may be due to lack of IgM support [24] or production of polyreactive, but nonspecific, IgG antibodies [25]. As a result, a functional assay that measures the capacity of detected antibody to opsonize and kill pneumococcus has emerged as a potentially more specific surrogate marker.…”

“…Serologic measurement of IgG against the pneumococcal antigen using ELISA assays was the first surrogate used, with antibody levels greater than 0.2-0.35 mg/l thought to offer protection against vaccine-targeted serotypes [23]. However, the ELISA assay does not always predict serotype protection, especially in older adults and immunosuppressed populations [24,25]. This may be due to lack of IgM support [24] or production of polyreactive, but nonspecific, IgG antibodies [25].…”