The mechanism of action of recombinant IgG2/4 antibodies involves blocking of their target without the induction of effector functions. Examples are eculizumab (Soliris®), which is used clinically to block complement factor C5, as well as anti-human CD14 (r18D11) and anti-porcine CD14 (rMIL2) produced in our laboratory. So far, no proper IgG2/4 control antibody has been available for controlled validation of IgG2/4 antibody functions. Here, we describe the design of a recombinant control antibody (NHDL), which was generated by combining the variable light (V) and heavy (V) chains from two unrelated specificities. NHDL was readily expressed and purified as a stable IgG2/4 antibody, and showed no detectable specificity toward any putative antigen present in human or porcine blood. The approach of artificial V/V combination may be adopted for the design of other recombinant control antibodies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927768PMC
http://dx.doi.org/10.1080/19420862.2019.1686319DOI Listing

Publication Analysis

Top Keywords

igg2/4 antibodies
8
control antibody
8
igg2/4 antibody
8
design recombinant
8
recombinant control
8
antibody
5
igg2/4
5
nhdl recombinant
4
recombinant v/v
4
v/v hybrid
4

Similar Publications

Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25.

View Article and Find Full Text PDF

Background: SB12 is being developed as a proposed biosimilar to eculizumab reference product (RP), a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 complement protein. Binding to this protein inhibits complement-mediated intravascular hemolysis by blocking its cleavage into C5a and C5b. Eculizumab RP is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive, and neuromyelitis optica spectrum disorder in adult patients who are anti-aquaporin-4 antibody-positive.

View Article and Find Full Text PDF

Approximately 100,000 mother-to-child transmission (MTCT) events of HIV human milk feeding occur each year. However, only about 15% of infants milk-fed by untreated HIV+ mothers become infected, suggesting a protective effect of the milk itself. Infants ingest 10-10 maternal leukocytes daily milk, which remain functional beyond ingestion.

View Article and Find Full Text PDF

Natural antibody IgG levels are associated with HBeAg-positivity and seroconversion in chronic hepatitis B patients treated with entecavir.

Sci Rep

March 2022

Laboratory Branch, Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention (NCHHSTP), US Centers for Disease Control and Prevention (CDC), Atlanta, GA, 30329, USA.

B1 cell-derived natural antibodies are non-specific polyreactive antibodies and can activate the complement pathway leading to lysis of enveloped virus particles before activation of the adaptive immune response. We investigated the relationship between natural antibody levels and treatment outcomes of 126 treatment-naïve chronic hepatitis B (CHB) patients, who underwent entecavir (ETV) treatment. Serum IgG1-3 and complement C3 levels were significantly higher in HBeAg-positive patients.

View Article and Find Full Text PDF

Background: ABP 959 is one of the first proposed biosimilars to eculizumab reference product (RP), a recombinant IgG2/4 monoclonal antibody (mAb) that binds human C5 complement protein and inhibits C5 cleavage to C5a and C5b, preventing the generation of the terminal complement complex C5b-9. Eculizumab RP is approved for the treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, myasthenia gravis in patients who are anti-acetylcholine receptor antibody positive, and neuromyelitis optica spectrum disorder in patients who are anti-aquaporin-4 antibody positive.

Objectives: The objective of this work was to comparatively assess analytical (structural and functional) similarity between ABP 959 and eculizumab RP using sensitive, state-of-the art analytical methods capable of detecting minor differences in product quality attributes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!