Bactex, Inc.

American Cyanamid Company

American Cyanamid Co. and Bactex, Inc.

Charles C Brinton, Jr

Bruce Arthur Green

John C McMichael

Peter C Fusco

Sam C To

Mark Hanson

The invention relates to the isolation and cloning of the structural gene, hipP, for the NTHi pili serotype 5 and the LKP operon. The invention relates to DNA molecules capable of hybridizing to the DNA sequences of the Haemophilus influenzae genome related to the pili. The invention further relates to a DNA molecule which encodes a pili protein, particularly a tip adhesion protein. The DNA molecules of the invention can be used in a method for assaying a sample, such as a blood sample, for the presence of Haemophilus influenzae in the sample. Accordingly, the invention further relates to the use of the DNA molecules as a diagnostic. The invention also relates to a recombinant Haemophilus influenzae pili protein, such as a tip adhesion protein. The protein can be employed in a method for immunizing an animal, such as a human, as a therapeutic or diagnostic.

Sequence and analysis of LKP pilin structural genes and the LKP pili

Purified pili of serotype LKP9 through LKP16 and LKP18 through LKP20 from Haemophilus influenzae. There is further provided a purified multivalent intact pilus vaccine composition for protecting subjects against infections caused by piliated H. influenzae which comprises a pharmaceutically acceptable carrier and whole H. influenzae pili, designated vaccine pili, previously separated from other H. influenzae components, in an amount capable of raising the antibody level of the subject to a level sufficient to provide such protection, said vaccine comprising pili of at least one type selected from a group of pili types designated LKP9 through LKP16 and LKP18 through LKP20, said vaccine pili being agglutinable by antisera derived from LKP pili purified from at least one strain of H. influenzae. Methods of immunizing employing said vaccines are also provided.

Haemophilus influenzae pilus vaccines

The isolation and cloning of the structural gene, hifA, for the NTHi pili serotype 5 and the serotype 1 LKP operon, DNA molecules capable of hybridizing to the DNA sequences of the Haemophilus influenzae genome related to the serotype 1 LKP operon and DNA molecules which encode LKP proteins are described.

There is provided a vaccine composition for protecting subjects against infections caused by piliated Haemophilus influenzae organisms which comprises a pharmaceutically acceptable carrier and whole H. influenzae pili, designated vaccine pili, previously separated from other H. influenzae components, in an amount capable of raising the antibody level of the subject to a level sufficient to provide such protection said vaccine comprising pili of at least one type selected from a group of pili types designated LKP1 through LKP8 said vaccine pili being agglutinable by anti sera derived from pili derived from organisms of at least one strain of one of the following said types. Methods of utilizing said vaccines are also provided.

A lectin derived from the pili of piliated organisms, said lectin being non-covalently bindable to the pilus rod protein of said pili and separable therefrom by the action of aqueous sodium dodecyl sulfate, possessing a single binding site for binding to mammalian erythrocyte ghosts.

Novel lectins derived from bacterial pili

It has been found that immunologically related piliated organisms exhibit a hierarchic relationship wherein the cross-reactivity of the antisera to first pili against second pill in the series is greater for the senior members of the series than the cross-reactivity of the first pili with the corresponding antisera from second pili. This asymmetric relationship leads to the situation where the juniormost pili in the series may be utilized to detect the presence of all members of the family senior to it and conversely the seniormost pili may be utilized to protect against infection by all strains junior in the series.

Pili of neisseria and vaccine compositions containing same

There is provided a vaccine material capable of providing substantial levels of protection against urinary tract infection caused by Escherichia coli. The protecting means comprises pili of organisms having pili of the same pilic family as those on the infecting organism. Protection is given by administering the pili to the subject to be protected.

Vaccine composition for immunization against urinary tract infection

There are provided a crystalline and single rod products derivable from the Pili of Type 1 and Type 2 Neisseria gonorrhoese organisms. There are provided methods of growing said organisms to produce the maximum yield of Pili and procedures for purifying said Pili to produce said crystalline material. There are further provided methods of utilizing said Pili to determine the presence, in a system infectable by N. gonorrhoese organisms, of antibodies to the Pili of said organisms, and methods of serotyping said Pili. There is also provided a mode of utilizing said crystalline material to provide a substantial degree of immunization infection by N. gonorrhoese in mammalian systems susceptible to such infection.

Gonococcal Pili processes for the preparation thereof and the use

There are provided a crystalline and single rod products derivable from the Pili of Type 1 and Type 2 Neisseria gonorrhoeae organisms. There are provided methods of growing said organisms to produce the maximum yield of Pili and procedures for purifying said Pili to produce said crystalline material. There are further provided methods of utilizing said Pili to determine the presence, in a system infectable by N. gonorrhoeae organisms, of antibodies to the Pili of said organisms, and methods of serotyping said Pili. There is also provided a mode of utilizing said crystalline material to provide a substantial degree of immunization to infection by N. gonorrhoeae in mammalian systems susceptible to such infection.

There is provided a vaccine material capable of providing substantial levels of protection against human disease caused by infection with Escherichia coli. The protecting means comprises pili of the infecting organism. The protection is given either by administering the pili directly to the subject to be protected or to a pregnant or lactating female where protection of the newborn is desired.

Immunization against infection by Escherichia coli

Immunization of humans against enterotoxogenic infection by Escherichia

There is provided a vaccine material capable of providing a substantial level of protection against infection by enterotoxogenic organisms of Escherichia coli. The protecting means comprises pili of the infecting organism. The protection is given either by administering the pili directly to the subject to be protected or to a pregnant female where protection of the newborn is desired. In the case of piglets, where there is substantially no transplacental transfer of immunity from mother to offspring, the pili are administered to mothers, who are then caused to feed the offspring to be protected, whereby the immunization is transferred via the colostrum of the mother.

Growing community of inventors

Pittsburgh, PA, United States of America

Charles C Brinton, Jr