Neutralizing antibodies to influenza viruses

a technology of neutralizing antibodies and influenza viruses, applied in the field of neutralizing antibodies to influenza viruses, can solve problems such as molecules not being able to react with hemagglutination, and achieve the effect of not inhibiting hemagglutination

Inactive Publication Date: 2010-02-18
I2 PHARMA INC
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AI Technical Summary

Benefits of technology

[0015]In one aspect, the present invention concerns a molecule that can neutralize at least one subtype of an influenza virus and/or at least one isolate of an influenza virus. In one embodiment, the molecule is an antibody or an antibody-like molecule, wherein the molecule (i) neutralizes more than one subtype and/or more than one isolate of an influenza A virus, (ii) binds to a hemagglutinin (HA) antigen of the virus, and (iii) does not inhibit hemagglutination. In another embodiment, the molecule is a polypeptide comprising a VpreB sequence and/or a λ5 sequence. In one...

Problems solved by technology

In other embodiments, the molecule does not prevent the influe...

Method used

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  • Neutralizing antibodies to influenza viruses
  • Neutralizing antibodies to influenza viruses
  • Neutralizing antibodies to influenza viruses

Examples

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example 1

Antibody Libraries from Survivors of Prior Bird Flu Outbreaks and Preparation of Neutralizing Antibodies

[0252]The widespread incidence of H5N1 influenza viruses in bird populations poses risks to human health. Even though the virus has not yet adapted for facile transmission between humans, it can cause severe disease and often death. Here we report the generation of combinatorial antibody libraries from the bone marrow of five survivors of the recent H5N1 avian influenza outbreak in Turkey. To date, these libraries have yielded >300 unique antibodies against H5N1 viral antigens. Amongst these antibodies, we have identified several broadly reactive neutralizing antibodies that could be used for passive immunization against H5N1 virus or as guides for vaccine design. The large number of antibodies obtained from these survivors provides a detailed immunochemical analysis of individual human solutions to virus neutralization in the setting of an actual virulent influenza outbreak. Rema...

example 2

Generating Universal Influenza Vaccines

[0321]The goal of vaccine design against heterogeneous pathogens is to identify and design effective and broadly protective antigens. In the case of influenza, considerable historical efforts have gone into the empirical testing of conserved linear sequences and regions with little success. A plausible reason for these failures is a lack of knowledge that focused responses against antigenic test articles are actual bona fide productive sites for neutralization of an antigen on the pathogen in the setting of an actual infection. For influenza one would be expect to find these bona fide solutions within the repertoires of survivors of an influenza infection. In our case we have demonstrated that several related antibodies amongst a large collection of antibodies, derived from an H5N1 influenza survivor, (see Table 4 above) are capable of broadly neutralizing several subtypes of Influenza. These antibodies neutralize influenza through a novel mech...

example 3

Increasing the Potency and Spectrum of Cross Subtype Neutralizing Antibodies

[0340]As mentioned previously, the group of cross subtype neutralizing antibodies that are partially represented by Ab-1, 2, & 3 contain very distinct and seemingly requisite heavy chain mutations within CDR2 and framework 3 (FR3), yet remarkably little to no diversity within CDR3. Considering the shear number of clones that were identified with these hallmark sequences, all of which were restricted to a 1-e, or 1-e like frameworks, leads one to suspect that this broad spectrum activity is principally driven by the this specific heavy chain framework and the CDR2 and Framework 3 (FR3) mutations. Recently, two groups have confirmed this at a structural level by analyzing co-crystals of hemagglutinin and other broad spectrum antibodies that utilize the 1-e like, 1-69 germline framework (Kashyap et al. supra; Throsby et al., PLoS ONE 3(12): e3942). In each instance the predominant binding was driven by CDR2 and...

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Abstract

The present invention concerns methods and means for identifying, producing, and engineering neutralizing molecules against influenza A viruses, and to the neutralizing molecules produced. In particular, the invention concerns neutralizing molecules against various influenza A virus subtypes, including neutralizing antibodies against H5 and/or H3 and/or H1, such as, for example all of H1, H3, and H5 subtypes, and methods and means for making such molecules.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority under Section §119(e) and the benefit of U.S. Provisional Application Ser. No. 61 / 040,459 filed Mar. 28, 2008, the disclosure of which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention concerns methods and means for identifying, producing, and engineering neutralizing molecules against viral antigens, including influenza A viruses, and to the neutralizing molecules produced. The invention further concerns various uses of the molecules produced, including the design and production of vaccines utilizing the binding sites of the neutralizing molecules of the present invention on the target viral antigen, such as influenza A virus.[0003]Viruses are infectious pathogens that can cause serious diseases including major threats for global public health, such as the influenza, AIDS, and hepatitis. A number of cancers have also been linked to viruses in conjunction...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K16/00A61P31/16C12Q1/70C40B40/10
CPCA61K39/00A61K2039/545C07K16/1018C07K2316/96C07K2317/21C12N2760/16111C07K2317/56C07K2317/565C07K2317/567C07K2317/622C07K2317/92C07K2317/55C07K2317/76A61P31/16A61P37/04A61K39/145A61K39/42A61K2039/505C12N7/00C12N2760/16134
Inventor HOROWITZ, LAWRENCEBHATT, RAMESHKASHYAP, ARUN
Owner I2 PHARMA INC
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