Functional antibodies to Haemophilus influenzae type B, Neisseria meningitidis, and Streptococcus pneumoniae contained in intravenous immunoglobulin products

Lee, So‐Young; Kim, Han Wool; Kim, Kyung Hyo

doi:10.1111/trf.13869

Cited by 13 publications

(21 citation statements)

References 33 publications

(45 reference statements)

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“…Of note, anti‐TNF therapies are associated with an increased risk of tuberculosis—consistent with the idea that inhibition of MAIT cell activation by anti‐TNF therapies might contribute to this process . Finally, most of the commercial intravenous immunoglobulin G products, used for example in patients with primary antibody deficiency, contain specific antibodies against a range of pathogens . Thus, an IgG‐mediated enhancement of MAIT cell function might also be included in the mode of action of intravenous immunoglobulin G therapy.…”

Section: Discussionmentioning

confidence: 99%

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

et al. 2019

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Mucosal‐associated invariant T (MAIT) cells are an abundant human T‐cell subset with antimicrobial properties. They can respond to bacteria presented via antigen‐presenting cells (APCs) such as macrophages, which present bacterially derived ligands from the riboflavin synthesis pathway on MR1. Moreover, MAIT cells are also highly responsive to cytokines which enhance and even substitute for T‐cell receptor‐mediated signaling. The mechanisms leading to an efficient presentation of bacteria to MAIT cells by APCs have not been fully elucidated. Here, we showed that the monocytic cell line THP‐1 and B cells activated MAIT cells differentially in response to Escherichia coli. THP‐1 cells were generally more potent in inducing IFNγ and IFNγ/TNF production by MAIT cells. Furthermore, THP‐1, but not B, cells produced TNF upon bacterial stimulation, which in turn supported IFNγ production by MAIT cells. Finally, we addressed the role of antibody‐dependent opsonization of bacteria in the activation of MAIT cells using in vitro models. We found that opsonization had a substantial impact on downstream MAIT cell activation by monocytes. This was associated with enhanced activation of monocytes and increased TNF release. Importantly, this TNF acted in concert with other cytokines to drive MAIT cell activation. These data indicate both a significant interaction between adaptive and innate immunity in the response to bacteria, and an important role for TNF in MAIT cell triggering.

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Section: Discussionmentioning

confidence: 99%

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

et al. 2019

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“…Overall, studies using OPA demonstrated trends that were similar to those of studies of pneumococcal antibody levels, with findings of low lot‐to‐lot variability from individual manufacturers and significant variability in opsonic activity among the products of different manufacturers …”

Section: Pneumococcal Antibodies In Immunoglobulin Productsmentioning

confidence: 99%

Measuring quantity and function of pneumococcal antibodies in immunoglobulin products

LaFon

Nahm

2018

Transfusion

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BACKGROUND Immunoglobulin replacement therapy is a cornerstone of the treatment of primary immunodeficiencies. Preparations used for replacement therapy are processed by purifying immunoglobulins from large pools of plasma, which were obtained from healthy donors. The constituent antibodies in these products depend on the immune history of the donor pool as well as manufacturing processes that differ among manufacturers. For these reasons various methods have been proposed to examine the levels and function of antibodies to organisms such as Streptococcus pneumoniae, which frequently causes infections in patients with immunodeficiencies. Pneumococcal antibody levels or antibody function can be measured with enzyme‐linked immunosorbent assay (ELISA) or multiplexed opsonophagocytosis assay (MOPA). Although these assays were developed initially to assess the immunogenicity of pneumococcal vaccines, the techniques have been adapted to evaluate immunoglobulin products as well. STUDY DESIGN AND METHODS This article provides a concise review of the analytic techniques for measuring pneumococcal antibodies and prior studies of immunoglobulin products utilizing these methods. RESULTS Studies utilizing these assays have demonstrated that antibody levels of immunoglobulin products can vary with time, location, and manufacturer. CONCLUSIONS We highlight current issues and future considerations concerning measurement of pneumococcal antibodies in immunoglobulin products, and the assays used for this purpose.

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“…Table presents data on antibodies to bacterial antigens from several studies of multiple lots of products produced in the US, UK, and EU . Antibodies against tetanus and diphtheria toxins are in the same range in 3 of the 4 studies which report them, but the results reported by Wu et al for products made from US source plasma seem to represent outliers, perhaps due to technical differences in the way the ELISAs were performed in that laboratory.…”

Section: Antibodies Against Common Bacterial Pathogens and Toxinsmentioning

confidence: 99%

“…In separate studies, Lee et al examined specific antibodies against H.influenzae polysaccharides in multiple lots of two Korean products . The mean contents of specific antibodies against H. influenzae polyribosyl‐phosphate, 0.29 and 0.27 μg/mg total IgG for the different products, are in good agreement with the data for Western products.…”

Section: Antibodies Against Common Bacterial Pathogens and Toxinsmentioning

confidence: 99%

“…The mean contents of specific antibodies against H. influenzae polyribosyl‐phosphate, 0.29 and 0.27 μg/mg total IgG for the different products, are in good agreement with the data for Western products. Assuming a dose of 400 mg IgG/kg in PIDD patients, calculations in the paper estimate that trough serum levels with all lots of both products would exceed the minimal protective level of 0.15 μg/ml …”

Section: Antibodies Against Common Bacterial Pathogens and Toxinsmentioning

confidence: 99%

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Antibodies to vaccine antigens in pooled polyclonal human IgG products

Berger¹

2018

Transfusion

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Immune‐deficient patients depend on the antibodies in pooled human immunoglobulin G (IgG) preparations to remain free from serious infections. The potency of IgG preparations is therefore an ongoing concern. The use of pooled IgG to prevent infection is based on the concept that healthy adults have recovered from infections earlier in life and maintain relatively high antibody titers. In general, vaccine‐induced immunity is less robust or long‐lasting than immunity after natural infection, and many infectious diseases which were formerly widely prevalent have become much less common due to improved hygiene and vaccines. This raises questions as to the adequacy of protective antibodies in current IgG preparations. This paper reviews available data on antibodies against selected bacterial and virus vaccine antigens in current IgG products. Most products contain sufficient antibody to yield levels above minimal protective concentrations to a broad range of pathogens and toxins. Illustrative examples of effects of vaccines on antibody content of IgG products are also discussed: antibody titers to hepatitis A virus in donor plasma pools in both the US and EU are dropping due to decreased natural infection, but they are still sufficient to provide robust protection. Increasing seroprevalence of hepatitis B virus as a result of immunization suggests that antibody titers against this virus may actually be increasing. Finally, serial studies suggest that pooled IgG provides protection against seasonal influenza viruses despite year‐to‐year antigenic drift, and is also likely to provide at least some protective antibody against potentially pandemic strains.

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Functional antibodies to Haemophilus influenzae type B, Neisseria meningitidis, and Streptococcus pneumoniae contained in intravenous immunoglobulin products

Abstract: Most of the tested commercial IVIG products had sufficient functional antibodies against Hib, pneumococcus, and meningococcus to protect patients with PAD receiving IVIG treatment. Regular and continuous evaluation of IVIG products is necessary to maintain an optimal therapeutic effect.

Cited by 13 publications

References 33 publications

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF‐dependent mechanism

Measuring quantity and function of pneumococcal antibodies in immunoglobulin products

Antibodies to vaccine antigens in pooled polyclonal human IgG products

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