Compositions that include hemagglutinin, methods of making and methods of use thereof

Abstract

Methods of making compositions that stimulate a protective immune response in a subject include a portion of a protein from a naturally occurring viral hemagglutinin, wherein the portion includes at least a portion of a globular head, includes at least a portion of at least one secondary structure that causes the globular head to essentially retain its tertiary structure, and lacks a membrane fusion domain, a transmembrane domain and a cytoplasmic domain. Compositions comprise a flagellin component or a Toll-like Receptor agonist component that is at least a portion of a flagellin or a Toll-like Receptor agonist, wherein the flagellin component or Toll-like Receptor agonist component includes at least one cysteine residue and whereby the flagellin component or Toll-like Receptor agonist component activates a Toll-like Receptor 5 or Toll-like Receptor. Compositions comprise a flagellin component that is at least a portion of a flagellin, wherein at least one lysine of the flagellin component has been substituted with at least one arginine, serine and histidine, whereby the flagellin component activates Toll-like Receptor 5. Compositions can further include an antigen, such as an influenza antigen, a flavivirus antigen, a pathogen-related antigen, a bacterial capsular antigen and a carrier protein. The compositions are used to stimulate an immune response and a protective immune response in a subject.

Description

[0001] Related applications [0002] This application is U.S. Provisional Application Nos. 60 / 779,854 (filed March 7, 2006), 60 / 784,497 (filed March 20, 2006), 60 / 790,457 (filed April 7, 2006) ), No. 60 / 814,292 (filed on June 16, 2006), No. 60 / 830,881 (filed on July 14, 2006), No. 60 / 838,007 (filed on August 16, 2006), and No. 60 / 838,007 (filed on August 16, 2006), and 856,451 (filed Nov. 3, 2006) and claims priority thereto. The entire teachings of the above application are incorporated herein by reference. Background technique [0003] Influenza virus infection can cause illness. Strategies for the prevention and management of diseases associated with influenza virus infection may include vaccination with inactivated viruses and drugs. However, such strategies may cost money to maintain needed supplies, and thus are in limited supply; may result in variable protection and unsatisfactory symptom reduction, and are therefore ineffective in preventing or treating disease asso...

AI Technical Summary

Problems solved by technology

However, such strategies may cost money to maintain needed supplies, and thus are in limited supply; may result in variable protection and unsatisfactory symptom reduction, and are therefore ineffective in preventing or treating disease associated with influenza virus infection Discomfort and consequences (in some cases death)

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