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Anti-staphylococcus aureus antibody combination preparation

A staphylococcus, golden yellow technology, applied in the direction of antibodies, antibacterial drugs, antibacterial immunoglobulin, etc., can solve problems such as adverse effects of vitality

Inactive Publication Date: 2018-04-03
ARSANIS BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In addition to leukocidin, an α-toxin (α-hemolysin, Hla) that targets epithelial and endothelial cells also induces inflammation, and although it does not directly lyse PMNs and macrophages, it is harmful to these cells and those Viability of undifferentiated immune cells has adverse effects

Method used

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Examples

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example 1

[1888] Example 1: Synergistic protective effect of antibody combinations neutralizing recombinant Staphylococcus aureus leukocidin mixture

[1889] The synergistic effect of the toxin cross-reactive mAb ASN-1 (Rouha, 2015) was demonstrated using a series of antibodies comprising the CDR sequences of AB-28 or its variant AB-28-x. An antibody comprising the CDR sequences of AB-28 or its variant AB-28-x (eg, an antibody of Table 1) is referred to herein as ASN-1. Such mAbs neutralize alpha-hemolysin, LukSF, LukED, HlgAB and HlgCB.

[1890] ASN-1 mAb was tested alone or with the LukGH neutralizing antibody ASN-2.

[1891] In the present invention, LukGH comprising the CDR sequences of AB-29, AB-30, AB-31, AB-32, AB-33, AB-34, AB-35 and AB-36 or a variant of any of the foregoing Neutralizing antibodies are referred to as ASN-2 mAbs, such as those in Table 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7 or 2.8.

[1892] Examples employ a series of CDR sequences comprising AB-30, AB-31, AB-32...

example 2

[1997] Example 2: Protection of human PMNs from Staphylococcus aureus culture supernatant mediated by toxin neutralizing antibody combinations to kill

[1998] The number of toxins encoded by genome-different S. aureus strains ranged from three to five, and the lukSF and lukED genes were not present in all strains. S. aureus secretes cytolytic leukocidins into the culture supernatant, and their levels in the supernatant are usually highest during the stationary growth phase.

[1999] According to this example, any mAb with the designation AB-28, AB-28-10, AB-28-7, AB-28-8 or AB-28-9 is compatible with the designation AB-30-3, AB-31, AB - Any mAb combination of 32-9, AB-34-6 or AB-34.

[2000] To test the independent and combined inhibitory ability of antitoxin mAbs on secreted exotoxins, bacterial culture supernatants (CS) were formulated in RPMI supplemented with 1% casamino acids (Amresco). Bacteria were cultured from a single colony to a stationary phase in 20 ml medi...

example 3

[2007] Example 3. Toxin neutralizing antibody combination prevents the toxin produced by live cells of Staphylococcus aureus from killing human PMN

[2008] It has been reported that Staphylococcus aureus can upregulate the expression of leukocidin when it encounters human PMN (Malachowa, 2011). Therefore, it is very interesting to test whether toxin-neutralizing antibodies are able to counteract the effects of bacterial toxins not only after pre-incubation of pre-formed toxins in culture supernatants, but also of bacterial toxins produced in situ in response to human phagocytes. important. For this purpose, PMNs were infected with live bacteria, and the viable cells were detected by flow cytometry to determine their viability.

[2009] Purified PMNs derived from human heparinized whole blood were diluted to 4x10 in RPMI supplemented with 10% FBS and L-glutamine 6 cells / mL. Staphylococcus aureus strains were grown to mid-log phase at 37°C with 200 rpm shaking (NewBrunswic...

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Abstract

An anti-Staphylococcus aureus antibody combination preparation comprising a) a toxin cross-neutralizing antibody comprising at least one polyspecific binding site that binds to alpha-toxin (Hla) and at least one of the bi-component toxins selected from the group consisting of HIg AB, HIg CB, LukSF, LukED, Luk S-Hlg B, LukSD, HIg A-LukD, HIg A-LukF, Luk EF, LukE-Hlg B, HIg C-LukD and HIg C-LukF; and b) an anti-Luk GH antibody;; and / or c) an OPK antibody which recognizes a S. aureus surface protein thereby inducing OPK, specifically an anti-Ig-binding protein (IGBP) antibody comprising at leastone CDR binding site recognizing any of the S. aureus Ig G binding domains of Protein A or Sbi.

Description

[0001] The present invention relates to a combination of isolated antibodies against Staphylococcus aureus with specific characteristics targeting alpha toxin, leukocidin and optionally anti-Ig-binding protein (IGBP) and / or the surface of Staphylococcus aureus protein. Background technique [0002] Staphylococcus aureus is a highly multifunctional opportunistic pathogen with diverse and complex pathogenesis. It is usually a harmless colonizer found in 25-30% of people in the anterior nares, skin, intestines and throat. When this "peaceful" coexistence is disturbed, Staphylococcus aureus can become a potent pathogen capable of causing infections in nearly all tissues, most commonly skin and soft tissue infections, pneumonia, bacteremia and sepsis (Lowy, 1998). Staphylococcus aureus is the most common cause of hospital wound infections, catheter-, prosthetic device and ventilator-associated infections. Although repeated exposure to S. aureus and mild infections do induce anti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/12A61K39/395A61P31/04
CPCC07K16/1271A61K2039/507C07K2317/76C07K2317/33A61P31/04C07K2317/31
Inventor E·纳吉A·巴达罗H·劳哈L·斯图利克Z·维斯拉姆
Owner ARSANIS BIOSCI
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