Washington University

Connaught Laboratories Limited

Her Majesty the Queen in Right of Canada, As Represented by the Minister

Robert S Munson, Jr

Michel Henri Klein

Pele Chong

Raafat Emil Fahim

Patrick McVerry

Susan Grass

Yan-Ping Yang

Dwo Yan Charles Sia

Josee Hamel

Robert Tolan

Bernard R Brodeur

The gene for outer membrane protein P1 of Haemophilus influenzae b is expressed in E. coli. Methods for expression and demonstration of the immunogenicity of recombinant P1 and portions thereof are disclosed, along with an improved method for the purification of P1. The nucleotide sequence of the P1 gene and the derived amino acid sequence of the P1 protein of Haemophilus influenzae type b are disclosed and the methods used to determine the same. Also disclosed are the methods used to clone and express the P1 gene as well as the purification protocol for the P1 gene products (recombinant P1 and P1 fusion proteins). Fourteen peptides are synthesized corresponding to specific sequences of the mature P1 protein. The use of the P1 protein as n immunogens for immunization against the disease caused by Haemophilus influenzae type b and the use of the protein as a carrier for conjugation with an oligosaccharide derived from Haemophilus to generate a potentially efficacious vaccine against the disease, are described. Also disclosed is the use of P1 peptide-conjugates as immunizing agents to elicit anti-Haemophilus influenzae type b antibodies.

Outer membrane protein P1 and peptides of Haemophilus influenzae type B

The nucleotide sequence of the P2 gene and the derived amino acid sequence of the P2 protein of Haemophilus influenzae type b are disclosed and the methods used to determine the same. Also disclosed are the methods used to clone and express the P2 gene as well as the purification protocol for the gene and protein. Also disclosed is the synthesis of peptides corresponding to the N-terminal and C-terminal ends of the P2 protein. Also disclosed is the use of the P2 protein as a protective agent for the disease caused by Haemophilus influenzae type b and the use of the protein as a carrier for conjugation with an oligosaccharide derived from Haemophilus to generate a potentially efficacious vaccine against the disease. Also disclosed is the use of P2 peptide-conjugates as immunising agents.

Membrane proteins and peptides of haemophilus influenzae type B

Murine monoclonal antibodies directed against a novel outer membrane protein (OMP) of Haemophilus influenzae have been isolated and characterized. The gene encoding of the outer membrane protein has also been isolated and characterized. Portions of the DNA sequence of the 15 kD OMP gene are useful as probes to diagnose the presence of Haemophilus influenzae in samples. These DNA's also make available polypeptide sequences of immunoreactive epitopes encoded within the gene, thus permitting the production of polypeptides which are useful as standards or reagents in diagnostic tests and/or as components of vaccines. Monoclonal antibodies directed against epitopes of the 15 kD OMP are also useful for diagnostic tests and as therapeutic agents for passive immunization.

DNA encoding the 15kD outer membrane protein of Haemophilus influenzae

Growing community of inventors

Ballwin, MO, United States of America

Robert S Munson, Jr