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Antibodies against human cytomegalovirus (hcmv)

一种抗体、抗体片段的技术，应用在抗病毒剂、抗病毒免疫球蛋白、抗体等方向，能够解决没有发现临床有效性等问题

Inactive Publication Date: 2010-01-13
RIBOVAX BIOTECHNOLOGIES SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, since no clinical effectiveness has been found in studies evaluating the efficacy of such antibodies, for example in hematopoietic stem cell transplantation (Boeckh M et al., 2001), or retinitis (GilpinA et al., 2003), it is used for Development of previously identified human antibodies for hCMV therapy (Matsumoto Y et al., 1986) has been discontinued

Method used

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  • Antibodies against human cytomegalovirus (hcmv)
  • Antibodies against human cytomegalovirus (hcmv)
  • Antibodies against human cytomegalovirus (hcmv)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Example 1: Culture of cells secreting human monoclonal antibodies that neutralize hCMV infectivity production of things

[0093] Materials and Methods

[0094] Selection of human donors with hCMV-neutralizing IgG antibodies in serum

[0095]hCMV-specific detection was performed as outlined in PCT / EP2005 / 056871 and in the literature summarized below.

[0096] hCMV neutralizing antibodies were detected according to the hCMV microneutralization assay based on human embryonic lung fibroblasts (HELF cells) and hCMV AD 169 strain (ATCC laboratory strain of hCMV, number VR-538).

[0097] It can also be performed using the endotheliotropic hCMV VR1814 strain (Revello M et al., 2001) and human umbilical vein endothelial cells (HUVEC) as progeny of clinical isolates recovered from cervical swabs of pregnant women. hCMV microneutralization test. Enzyme treatment of the umbilical cord vein and growth in the presence of 2% fetal bovine serum (FBS), recombinant human vascula...

Embodiment 2

[0121] Example 2: Identification of 26A1 Antibody

[0122] Materials and methods

[0123] Expansion and identification of 26A1 subculture

[0124] Cells from the original subculture 26A1 were expanded on radioactive allogeneic PBMCs in IMDM medium (supplemented with 10% FCS and NEAA), using during this expansion step as described in Example 1 The hCMV microneutralization assay confirmed hCMV neutralizing activity at least twice (see Table 1).

[0125] The amount of antibody secreted by 26A1 subcultures at 24, 48 and 72 hours was determined using a commercially available quantitative human IgG ELISA kit (Immunotek; Cat. No. 0801182; Zeptometrix Corp.) according to the manufacturer's instructions. The subclass of the 26A1 antibody was determined using a commercially available assay (PeliClass human IgG subclass ELISA combi-kit; number #RDI-M155lcib, RDI Division of Fitzgerald Industries Intl.).

[0126] Cells contained in 1 well of a 96-well plate (≈1 × 10 5 ) were inocu...

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Abstract

The present invention provides novel antibody sequences that bind human cytomegalovirus (hCMV) and neutralize hCMV infection. The novel sequences can be used for the medical management of hCMV infections, in particular for preparing pharmaceutical compositions to be used in the prophylactic or therapeutic treatment of hCMV infections.

Description

technical field [0001] The present invention relates to novel antibody sequences isolated from human B cells having specific biological activity against viruses that infect human cells. Background technique [0002] Human cytomegalovirus (hCMV) is a widespread, highly species-specific herpesvirus that causes high morbidity and mortality in immunosuppressed or immunocompromised individuals. [0003] Several recent literature reviews have analyzed the biological and clinical manifestations of hCMV (Landolfo S et al, 2003; Gandhi M and Khanna R, 2004; Soderberg-Naucler C, 2006a). This viral pathogen infects most of the world's population and is acquired during childhood after exposure to body fluids, as the virus enters through endothelial or epithelial cells of the upper gastrointestinal or respiratory system, or through the genitourinary system. Seropositivity for hCMV is more common in developing countries or low-income regions. [0004] After primary infection, hCMV can e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/06C07K16/00C07K16/08
CPCC07K2317/21A61K38/00C07K16/088A61K31/7088C07K2317/56C07K2316/96C07K2317/76A61P31/12A61P31/20C07K16/089C07K16/08C12N15/11A61K39/395
Inventor 阿达·富纳罗乔治·格里包多桑托·兰多尔福
Owner RIBOVAX BIOTECHNOLOGIES SA
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