North American Vaccine, Inc.

The Rockefeller University

Baxter International Inc.

Merck + Co., Inc.

Joseph Y Tai

Milan S Blake

Francis Michon

Shu-Mei Liang

Jeffrey K Pullen

Lucjan J Hronowski

Huilin L Qi

John B Zabriskie

Catherine Uitz

Richard L Tolman

Maurice R Hilleman

Philip P Vella

Mary Ellen Polvino-Bodnar

Thomas Soper

Catherine Dong

Conceicao Minetti

Sharon Mates

This invention provides a novel immunogenic composition and vaccine, processes for producing them and methods for immunization against infections and disease caused by group A Streptococci. The compositions include group A streptococcal polysaccharide covalently linked to protein or liposomes to form immunogenic conjugates. The method of immunization for this invention comprises administering to an individual an immunogenic amount of group A polysaccharide. The group A polysaccharide may be administered as a vaccine either on its own, conjugated to proteins or conjugated to liposomes. Additionally, the group A polysaccharides may be associated with an adjuvant. This invention is particularly useful for providing both active and passive immunogenic protection for those populations most at risk of contracting group A Streptococcal infections and disease namely adults, pregnant women and in particular infants and children.

Group A streptococcal polysaccharide immunogenic compositions and methods

This invention relates to modified pneumolysin polypeptides that retain the immunogenic nature of pneumolysin but have reduced or undetectable hemolytic activity compared to native pneumolysin. The invention also provides a method for generating novel pneumolysin variants with these desired characteristic properties. The invention also provides immunogenic compositions useful as pharmaceutical compositions including vaccines in which non-toxic, modified pneumolysin is used to stimulate protective immunity against The vaccines may be compositions in which the modified pneumolysin is conjugated to bacterial polysaccharides or may be carried on an attenuated viral vector. In addition, the invention also provides a method of using the non-toxic, modified pneumolysin toxoid in order to stimulate antibodies against in a treated individual which are then isolated and transferred to a second individual, thereby conferring protection against in the second individual.

Modified immunogenic pneumolysin compositions as vaccines

The process for depolymerizing Group B Types II and III streptococcal polysaccharide is disclosed which results in polysaccharide fragments having a reducing end suitable for conjugating to protein. Conjugate molecules, vaccines and their use to immunize mammals including humans are also disclosed.

Method of immunization using a Group B Streptococcus type II and type III polysaccharide conjugate vaccine

The process for depolymerizing Group B Types II and III Streptococcal Polysaccharide is disclosed which results in polysaccharide fragments having a reducing end suitable for conjugating to protein. Conjugate molecules, vaccines and their use to immunize mammals including humans are also disclosed.

Antigenic group B Streptococcus type II and type III polysaccharide fragments having a 2, 5-anhydro-D-mannose terminal structure and conjugate vaccine thereof

The process for depolymerizing Group B Types II and III Streptococcus is disclosed which results in polysaccharide fragments having a reducing end suitable for conjugating to protein. Conjugate molecules, vaccines and their use to immunize mammals including humans are also disclosed.

Antigenic group B streptococcus type II and type III polysaccharide fragments having a 2,5-anhydro-D-mannose terminal structure and conjugate vaccine thereof

A-X,X,X,X,X,X,X,X,X,X,X,X,-B, wherein A represents amino acid residues 38-201 of SEQ ID NO: 2, B represents a sequence starting from amino acid 214 of SEQ ID NO: 2 and terminating at an amino acid between residues 1131 and 1164, inclusive, of SEQ ID NO: 2, and X,through X,are each selected independently from Ala, Val, Leu, Ile, Pro, Met, Phe, Trp, a bond, or a wild-type amino acid as found at a corresponding position of residues 202-213 of SEQ ID NO: 2, with the proviso that at least one of X,through X,, inclusive, is other than the wild type amino acid found at the corresponding position of SEQ ID NO: 2. The LPXTG motif, as found in the native protein at amino acid residues corresponding to residues 1132-1136 of SEQ ID NO: 2, may be deleted in the sequence of the mutant C&bgr; protein. The mutant C&bgr; protein is conjugated to a streptococcal capsular polysacharide in a vaccine composition, also having an acceptable pharmaceutical carrier, for use in a method of including an immune response in an animal. Nucleic acid molecules encoding the mutant protein, vectors containing these molecules, and host cells transformed therewith are also disclosed.

Non-IgA Fc binding forms of the group B streptococcal &bgr; antigens

The present invention relates, in general, to a method of expressing the outer membrane protein P2 from Haemophilus influenzae type b (Hib-P2) and fusion proteins thereof. In particular, the present invention relates to a method of expressing the outer membrane protein P2 from Haemophilus influenzae type b or fusion protein thereof in E. coli wherein the Hib-P2 protein or fusion protein comprises more than 2% of the total protein expressed in E. coli. The invention also relates to a method of purification and refolding of Hib-P2 protein and fusion protein thereof.

Method for the high level expression, purification and refolding of the

The present invention relates, in general, to a method for the high level expression of the outer membrane protein meningococcal group B porin proteins and fusion proteins thereof. In particular, the present invention relates to a method of expressing the outer membrane protein meningococcal group B porin proteins in E. coli wherein the meningococcal group B porin proteins and fusion proteins thereof comprise more than 2% of the total protein expressed in E. coli. The invention also relates to a method of purification and refolding of the meningococcal group B porin proteins and fusion proteins thereof and to their use in vaccines.

The present invention relates, in general, to a method for the high level expression of the outer membrane protein meningococcal group B porin proteins and fusion proteins thereof. In particular, the present invention relates to a method of expressing the outer membrane protein meningococcal group B porin proteins in E. coli wherein the meningococcal group B porin proteins yard fusion proteins thereof comprise more than 2% of the total protein expressed in E. coli. The invention also relates to a method of purification and refolding of the meningococcal group B porin proteins and fusion proteins thereof and to their use in vaccines.

An immunogenic conjugate comprising a modified group C meningococcal polysaccharide (GCMP) coupled to a carrier molecule. The GCMP is modified by O-deacetylation to a varying extent. This modified GCMP conjugate stimulates a strong immunogenic response. The antiserum, produced by immunization with this conjugate, is cross-reactive with the native polysaccharide. In addition, these antisera elicit a class of antibodies that have patent bactericidal activity.

Vaccines against group C Neisseria meningitidis

Haemophilus influenzae type B polysaccharide is coupled through a spacer to a serotype outer membrane protein from Neisseria meningitidis. This conjugate has enhanced antigenicity and immunogenicity relative to the unconjugated polysaccharide.

Growing community of inventors

Fort Washington, PA, United States of America

Joseph Y Tai