Pre-fusion rsv f antigens

A pre-fusion, chimeric technology, applied in the direction of fusion peptides, viral antigen components, antiviral agents, etc., can solve the problem of not producing candidates

Inactive Publication Date: 2014-06-04
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, efforts to generate soluble, stabilized prefusion F subu...

Method used

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  • Pre-fusion rsv f antigens
  • Pre-fusion rsv f antigens
  • Pre-fusion rsv f antigens

Examples

Experimental program
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Embodiment

[0535] 1. Post-fusion structure and pre-fusion model

[0536] RSV F structure after fusion

[0537] A stable, non-aggregating soluble RSV F subunit antigen ( figure 1 ). This engineered F is efficiently expressed and easily purified. Electron micrographs of negatively stained samples show the formation of non-aggregated, uniform cane-shaped molecules, consistent with postfused F trimers ( figure 2 A). The engineered F trimer is stable, and the circular dichroism spectrum shows no obvious melting when the temperature is up to 95 °C ( figure 2 B and 2C).

[0538] The RSV F protein was crystallized, and its structure was determined by molecular substitution and three-fold non-crystallographic symmetry (NCS) averaging (Table 3 and image 3 ). The structure does not include the p27 fragment (peptide between the two furin sites, which is lost after cleavage), the fusion peptide, the transmembrane region and the cytoplasmic domain ( Figure 4 ).

[0539] Table 3. Crysta...

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Abstract

The invention relates to pre-fusion RSV F protein and polypeptides that contain one or more amino acid mutations that stabilize the pre-fusion conformation or destabilize the post-fusion conformation. The invention also relates to methods for inducing an immune response to pre-fusion RSV F.

Description

[0001] related application [0002] This application claims priority to US Provisional Application 61 / 486,005, filed May 13, 2011. The entire contents of the aforementioned applications are incorporated herein by reference. [0003] sequence listing [0004] This application contains a Sequence Listing submitted in ASCII format via EFS-Web, which is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 11, 2012, is named PAT05457.txt and is 98,385 bytes in size. Background of the invention [0005] Respiratory syncytial virus (RSV) is an enveloped non-segmented negative-sense RNA virus in the genus Pneumovirus of the Paramyxoviridae family. It is the leading cause of bronchiolitis and pneumonia in children's first year of life. RSV also causes superinfections including severe lower respiratory disease, which can occur at any age, especially in the elderly or those with compromised hearts, lungs or immune systems. [0006] To infect a host cell,...

Claims

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Application Information

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IPC IPC(8): C07K14/135
CPCA61K39/155C12N2760/18534C07K2319/735C12N2760/18522A61K2039/53C07K14/005A61K39/12A61P31/14
Inventor K·斯旺森A·卡尔菲
Owner NOVARTIS AG
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