Reduction in Functional Antibody Activity Against Streptococcus pneumoniae in Vaccinated Elderly Individuals Highly Correlates with Decreased IgG Antibody Avidity

Romero-Steiner, Sandra; Musher, Daniel M.; Cetron, Marty; Pais, Lorna B.; Groover, Jean E.; Fiore, Anthony E.; Plikaytis, Brian D.; Carlone, George M.

doi:10.1086/520200

Cited by 283 publications

(217 citation statements)

References 32 publications

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“…Owing to the delay and impairment of the immune response after HSCT, one may suspect that antibodies produced after vaccination by HSCT recipients may have a suboptimal opsonophagocytic activity. Discrepancies between ELISA results and OPA results have already been found in older children and adult populations, especially in the elderly 14 and in HIV patients. 15 Therefore, OPA data provide important additional information to assess the efficacy of PCV7 in an immunocompromised population such as HSCT patients, even in the absence of an established protective OPA titer cutoff in adults.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…This protocol was recommended by the World Health Organization at that time and was extensively used by experts (7,8,20). The pneumococcal capsular polysaccharide preparations used in the present ELISA are contaminated with a common cell wall (C-PS), and therefore antibodies to C-PS should be absorbed to improve the specificity of the ELISA (21).…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in Brazilian elderly

Simonsen

Brandão

Brandileone

et al. 2005

Braz J Med Biol Res

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Serum antibodies specific for the capsular polysaccharides of Streptococcus pneumoniae provide protection against invasive pneumococcal infection. In Brazil, this vaccine has been used for people over 65 years with clinical risk to develop pneumococcal infection since 1999. We evaluated the immune response of 102 elderly subjects (75.5% females and 24.5% males) with a mean age of 71 years, and 19 young healthy adults (63.2% females and 36.8% males) with a mean age of 27 years. The elderly study group consisted of outpatients who received follow-up care in the Geriatric Department of General Hospital, Faculty of Medicine, University of São Paulo. None had acute illness at the time of vaccination. Both groups were immunized with one intra-deltoid injection with 0.5 ml of a 23-valent pneumococcal polysaccharide vaccine. The total IgG specific antibody concentrations to capsular polysaccharides 1, 3, 5, 6B, 8, and 14 were determined against pre-and 1-month post-vaccination sera. All samples were analyzed according to the second-generation pneumococcal polysaccharide ELISA protocol. We observed that the pneumococcal polysaccharide vaccine evoked consistent antibody increase for serotypes 1, 5, 6B, 8, and 14 (geometric mean concentration increase of 2.46 in the elderly and 2.84 in the young adults). Otherwise, we observed no increase in antibody concentration for serotype 3 in both groups.

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“…This appears to be linked to the very limited genetic diversity of the immune response to polysaccharides. The elderly population appear to produce antibodies of lower avidity (Romero-Steiner et al 1999).…”

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confidence: 99%

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Jones

2005

An. Acad. Bras. Ciênc.

167

114

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Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development.This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

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Reduction in Functional Antibody Activity Against Streptococcus pneumoniae in Vaccinated Elderly Individuals Highly Correlates with Decreased IgG Antibody Avidity

Cited by 283 publications

References 32 publications

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

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

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in Brazilian elderly

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

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