Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies

Siber, George R.; Chang, Ih; Baker, Sherryl; Fernsten, Philip; O’Brien, Katherine L.; Santosham, Mathuram; Klugman, Keith P.; Madhi, Shabir А.; Paradiso, Peter R.; Kohberger, Robert

doi:10.1016/j.vaccine.2007.01.119

Cited by 317 publications

(228 citation statements)

References 27 publications

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“…After the analysis of 3 double-blind controlled VE trials, a concentration of IgG anti-capsular polysaccharide antibodies measured by ELISA 0.35 mg/ml was adopted as the protective threshold for all pneumococcal serotypes. 41 The analysis was based on the notion of VEI described above, but, since VE calculated with a clinical endpoint was known for all trials, the protective antibody threshold was directly determined from the reverse cumulative distribution curves 42 of the antibody concentrations of the vaccinated group and the control group. 41 …”

Section: Meningococcal Vaccinesmentioning

confidence: 99%

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges

Ángel

Steele

Franco

2014

Human Vaccines & Immunotherapeutics

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Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

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Section: Meningococcal Vaccinesmentioning

confidence: 99%

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges

Ángel

Steele

Franco

2014

Human Vaccines & Immunotherapeutics

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“…Serum pneumococcal IgG responses to the seven vaccine serotypes were determined by the WHO-standardized serotypespecific anti-pneumococcal capsular polysaccharide ELISA using pneumococcal C-polysaccharide and 22F to adsorb non-specific antibodies. 10,11 Pneumococcal IgG ELISA titers were expressed as mg/ml using the standard reference serum 89-SF.…”

Section: Serum Collection and Ab Measurementsmentioning

confidence: 99%

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

Cordonnier

Labopin

Jansen³

et al. 2009

Bone Marrow Transplant

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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...

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“…Other studies on the immunogenicity of pneumococcal conjugate vaccines in HIV-infected children have also been based on assumptions described for non-HIV-infected children while defi ning a protective antibody level. 4,5,13 However, in 2005, the World Health Organization (WHO) 16,20 defi ned a protective antibody level against pneumococcal invasive disease for healthy children immunized with a conjugate vaccine. Humoral response to the vaccine in healthy children was defi ned as titers equal to or greater than 0.35 μg/mL measured using ELISA within one month post-primary immunization.…”

Section: Discussionmentioning

confidence: 99%

“…This was assumed because, even in the largest study (the Kaiser Permanente included 37,868 children), 2 the number of cases of invasive disease was still small for each specifi c, preventing a serotype-specifi c effi cacy analysis. 16 King et al 4 in 1996, defi ned "evidence of humoral response" as a 4-fold increase or more in post-compared to pre-immunization antibody titers. A year later, 5 while investigating the same 5-valent vaccine, they chose to set the protective antibody titer at 1,0 μg/mL based on 1981 Landesman & Schiffman study.…”

Section: Discussionmentioning

confidence: 99%

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Avaliação da resposta humoral à vacina pneumocócica 7-valente em crianças com Aids

Costa¹,

Guilardi²,

Kmiliauskis³

et al. 2008

Rev. Saúde Pública

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OBJECTIVE:Invasive pneumococcal disease is a major cause of death in HIV-infected children. The objective of the study was to assess the quantitative antibody response to the seven pneumococcal serotypes of heptavalent pneumococcal conjugate vaccine in a group of HIV-infected children. METHODS:Study comprising 40 HIV-infected children aged between 2 and 9 years followed up in a specialized outpatient clinic in São Paulo, Brazil, between 2002 and 2003. Enzyme immunoassay (ELISA) was used to measure IgG antibody titers against pneumococcus capsule. Antibodies were measured immediately before and 1 month after the second dose of the vaccine. Two response criteria were used: IgG titers ≥1.3 μg/mL in the postimmunization serology and an increase of at least 4-fold in post-compared to pre-immunization serology. RESULTS:For the first criterion (≥1.3 μg/mL), 26 (65%) children had serological response to the vaccine, 12 (30%) showed post-immunization IgG titers of at least 1.3 μg/mL for all seven serotypes studied. For the second criterion studied (≥4-fold increase in post-compared to pre-immunization titers for four serotypes or more), serological response was seen in 15 (37.5%) children. CONCLUSIONS:Overall response to the heptavalent pneumococcal conjugate vaccine was adequate, showing a statistically signifi cant increase in the postimmunization geometric mean titers for the seven serotypes studied.

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Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies

Cited by 317 publications

References 27 publications

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges

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

Avaliação da resposta humoral à vacina pneumocócica 7-valente em crianças com Aids

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