Sanofi Pasteur Inc.

The Kingdom of the Netherlands, Represented by the Minister of Health, Welfare and Sport, on Behalf of the Minister, the National Institute of Public Health and the Environment

The Kingdom of the Netherlands, Represented by the Mininster of Health, Welfare and Sport, on Behalf of the Minster the National Institute of Public Health and the Environment

Raymond Oomen

Eliud Oloo

Tod Dwayne Strugnell

Jeremy Yethon

Martina Ochs-Onolemhemhen

Harold Kleanthous

Martina Ochs

Thorsten Vogel

The present invention provides, among other things, a novel and improved method for generating 'mosaic' influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered H1N1 influenza hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple H1N1 viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.

Engineered influenza antigenic polypeptides and immunogenic compositions thereof

The present invention provides, among other things, modified recombinant HA polypeptides with broadened immunogenic profile that extends coverage to antigenically distinct influenza strains and methods of making and using the same.

Modification of engineered influenza hemagglutinin polypeptides

The present disclosure relates to a cluster-based consensus approach for generating recombinant hemagglutinin (HA) polypeptides. The disclosure further relates to influenza vaccine compositions comprising the recombinant HA polypeptides.

Methods of generating broadly protective vaccine compositions comprising hemagglutinin

This disclosure relates to immunogenic compositions comprising mutantpneumolysin (PLY) proteins. Nucleic acids, polypeptides encoded thereby, compositions containing the same, methods for using such nucleic acids, polypeptides and compositions are also provided.

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This disclosure relates to modifiedpneumolysm (PLY) proteins which lack hemolytic activity and can be used as immunogens in an immunogenic composition or vaccine against invasive pneumococcol diseases caused byThe modified pneumolysm proteins comprise amino acid substitutions at threonine 65, glycine 293 and cysteine 428 Nucleic acids, polypeptides encoded thereby, compositions containing the same, methods for using such nucleic acids, polypeptides and compositions are also provided.

This disclosure relates to modifiedpneumolysm (PLY) proteins which lack hemolytic activity and can be used as immunogens in an immunogenic composition or vaccine against invasive pneumococcol diseases caused by. The modified pneumolysm proteins comprise ammo acid substitutions at threonine 65, glycine 293 and cysteine 428 Nucleic acids, polypeptides encoded thereby, compositions containing the same, methods for using such nucleic acids, polypeptides and compositions are also provided.

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Cambridge, MA, United States of America

Raymond Oomen