Glaxosmithkline Biologicals Sa

Novartis Vaccines & Diagnostics, Gmbh

Novartis Ag

Chiron Corporation

Seqirus UK Limited

Other

Fidia Farmaceutici S.p.a.

Novartis Vaccines and Diagonstics, Inc.

National Institutes of Health, Dhhs

Derek T O'Hagan

Manmohan Singh

Gary S Ott

Luis Brito

Andrew John Geall

Gary Van Nest

Jina Kazzaz

Siddhartha Jain

Barbara Baudner

John J Donnelly

John Barackman

Rino Rappuoli

Mildred Ugozzoli

Simone Bufali

Michelle Chan

Maninder S Hora

Mario Contorni

Nicholas M Valiante

Giuseppe Del Giudice

Nicola Groth

Padma Malyala

Alessandra Pavesio

David Skibinski

Janet Wendorf

Jia-Hwa Fang

Sung-Yun Kwon

Michelle C Archer

Michael Houghton

Mark J Selby

Dennis M Klinman

Susan Barnett

Christian Walter Mandl

Bret A Shirley

Sergio Abrignani

Michele Pallaoro

Edward Charles Lavelle

Ugo D'Oro

Jens Martin Heile

Mammohan Singh

Silvia Vendetti

Christian Mandi

David Skibinksi

Simona Gallorini

Sushma Kommareddy

Aravind Chakrapani

John Donnelly

Manmohan c/o Novartis Vaccines And Diagnostics Inc Singh

An immunogenic composition comprising: (i) a non-virion influenza virus antigen, prepared from a virus grown in cell culture; and (ii) an adjuvant. Preferred adjuvants comprise oil-in-water emulsions.

Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture

Nucleic acid immunisation is achieved by delivering a self-replicating RNA encapsulated within a small particle. The RNA encodes an immunogen of interest, and the particle may deliver this RNA by mimicking the delivery function of a natural RNA virus. Thus the invention provides a non-virion particle for in vivo delivery of RNA to a vertebrate cell, wherein the particle comprises a delivery material encapsulating a self-replicating RNA molecule which encodes an immunogen. These particles are useful as components in pharmaceutical compositions for immunising subjects against various diseases.

Virion-like delivery particles for self-replicating RNA molecules

Influenza vaccines include hemagglutinin from at least one influenza A virus strain and at least one influenza B virus strain. They also include an oil-in-water emulsion adjuvant with submicron oil droplets, comprising squalene. In some embodiments the hemagglutinin concentration is &#x3e;12 &#x3bc;g/ml per strain. In some embodiments the squalene concentration is &#x3c;19 mg/ml. In some embodiments the vaccine is mercury-free. In some embodiments the vaccine has a unit dose volume between 0.2-0.3 mL. In some embodiments the squalene concentration is 9.75 mg/mL or 4.88 mg/mL. In some embodiments the vaccine includes antigens from two influenza A virus strains and two influenza B virus strains.

Influenza vaccines with reduced amounts of squalene

Retinoic acid, or an analogue thereof, is delivered within an oil-in-water emulsion to provide an improved immunological adjuvant.

Oil-in-water emulsions including retinoic acid

This invention generally relates to cationic oil-in-water emulsions that contain high concentrations of cationic lipids and have a defined oil:lipid ratio. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines.

Cationic oil-in-water emulsions

This invention generally relates to cationic oil-in-water emulsions that can be used to deliver negatively charged molecules, such as an RNA molecule. The emulsion particles comprise an oil core and a cationic lipid. The cationic lipid can interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are particularly suitable for delivering nucleic acid molecules (such as an RNA molecule encoding an antigen) to cells and formulating nucleic acid-based vaccines.

Method for preparing composition comprising a cationic oil-in-water emulsion

This invention generally relates to cationic oil-in-water emulsions that can be used to deliver nucleic acid molecules, such as an RNA molecule. The emulsion particles comprise an oil core and a cationic lipid. The emulsion particles have an average diameter of about 80 nm to about 180 nm, and the emulsion have an N/P ratio of at least 1.1:1.

Oil-in-water emulsions that contain nucleic acids

The invention improves TdaP vaccines by including a TLR agonist in them. This agonist can provide stronger protection, longer-lasting protection, and/or can reduce the amount of antigen which is required to achieve a particular immune response.

Adjuvanted formulations of booster vaccines

An immunogenic composition comprising (i) a non-virion influenza virus antigen prepared from a virus grown in cell culture; and (ii) an adjuvant. Preferred adjuvants comprise oil-in-water emulsions.

Combination vaccine compositions as well as methods for their manufacture have a relatively low amount of antigen and/or a relatively low amount of aluminium, but they can nevertheless have immunogenicity which is comparable to combination vaccines with a relatively high amount of antigen and/or a relatively high amount of aluminium. Aluminium-free combination vaccine compositions are also provided e.g. compositions which are adjuvanted with an oil-in-water emulsion adjuvant.

Combination vaccines with lower doses of antigen and/or adjuvant

In one aspect, the present invention provides sterile microparticle compositions comprising biodegradable microparticles, which comprise at least one biodegradable polymer. In other aspects, the present invention provides methods of making and using such compositions as well as articles of manufacture and kits containing the same.

Irradiated biodegradable polymer microparticles

To formulate amphiphilic pharmacological agents (in particular, amphiphilic immunopotentiators) in oil-in-water emulsions the invention provides an oil-in-water emulsion comprising an aqueous phase, an oil phase, a surfactant, and a phospholipid.

Adjuvant nanoemulsions with phospholipids

High loading of lipophilic pharmacological agents (in particular, lipophilic immunopotentiators) in oil-in-water emulsions can result in crystallisation of the lipophilic agent. To overcome this problem the invention uses an oil-in-water emulsion in combination with a crystallisation inhibitor, and this combination provides emulsions which can be loaded with high levels of lipophilic pharmacological agents.

Adjuvant nanoemulsions with crystallisation inhibitors

Growing community of inventors

Berkeley, CA, United States of America

Derek T O'Hagan