Vaccine based on attenuated Haemophilus somnus

Details Vaccine based on attenuated Haemophilus somnus Vaccine based on attenuated Haemophilus somnus

2001-06-25

2004-08-03

Navarro, Mark (Department: 1645)

Drug, bio-affecting and body treating compositions

Whole live micro-organism, cell, or virus containing

C424S093200, C424S093400

Reexamination Certificate

active

06770273

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates generally to the prevention of diseases of cattle and, more specifically, to immunizing against such diseases by vaccination.
Bovine respiratory disease (BRD), bovine septicemia and bovine reproductive failure (BRF) result in great economic loss to the cattle industry. The primary bacterial pathogens implicated in BRD are
Pasteurella haemolytica, P. multocida
and
Haemophilus somnus. H. somnus
also causes bovine reproductive failure (BRF) and septicemia.
Current vaccines for
H. somnus
consist mainly of killed bacteria (bacterins) or bacterial extracts. Although there is evidence for protection in some controlled laboratory or animal challenge studies, efficacy in field studies is generally lacking. In some cases the vaccines cause such adverse side effects that their use is very limited. In other cases, little protection is seen. Thus, there is a need to develop improved vaccines to protect cattle from
H. somnus
mediated diseases. Such vaccines should contain key protective antigens that elicit appropriate antibody and cell-mediated immune responses. In addition, such vaccines should lack factors that cause adverse reactions and enable pathogens to evade immune recognition or effector mechanisms.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide an effective and safe
H. somnus
vaccine for protection against BRD, BRF, septicemia and related disorders.
To accomplish these and other objectives, there has been provided, in accordance with one aspect of the present invention, a method for vaccinating cattle against diseases mediated by infection, comprising administering an effective amount of an
H. somnus
vaccine, wherein the
H. somnus
is susceptible to killing by bovine complement-containing serum.
According to another embodiment of the present invention, the
H. somnus
is live.
According to another embodiment of the present invention, the
H. somnus
is killed.
According to yet another embodiment of the present invention, the
H. somnus
lacks the expression of one or more immunoglobulin binding proteins present in virulent
H. somnus
. In a further embodiment, the lack of expression of one or more immunoglobulin binding proteins is achieved by the step of genetically engineering
H. somnus
to delete genes encoding the immunoglobulin binding proteins.
According to still yet another embodiment of the present invention, the
H. somnus
expresses a protective antigen. In a further embodiment, the protective antigen is a 40 kDa outermembrane protein.
According to another embodiment of the present invention, the
H. somnus
releases reduced amounts of endotoxin during growth as compared to virulent
H. somnus.
According to yet another embodiment of the present invention, the
H. somnus
is selected from the group consisting of PTA-600, PTA-601, PTA-602 and PTA-603, all on deposit with the American Type Culture Collection.
In accordance with another aspect of the present invention, a method is provided for vaccinating cattle against diseases mediated by infection, comprising administering an effective amount of an
H. somnus
vaccine, wherein the
H. somnus
releases reduced amounts of endotoxin as compared to virulent
H. somnus.
According to another embodiment of the present invention, the
H. somnus
is live.
According to another embodiment of the present invention, the
H. somnus
is killed.
According to yet another embodiment of the present invention, the
H. somnus
is sensitive to killing by complement-containing bovine serum.
According to still yet another embodiment of the present invention, the
H. somnus
lacks the expression of one or more immunoglobulin binding proteins present in virulent
H. somnus
. In a further embodiment, the lack of expression of one or more immunoglobulin binding proteins is achieved by the step of genetically engineering
H. somnus
to delete genes encoding the immunoglobulin binding proteins.
According to another embodiment of the present invention, the
H. somnus
expresses a protective antigen. In a further embodiment, the protective antigen is a 40 kDa outermembrane protein.
According to yet another embodiment of the present invention, the
H. somnus
is selected from the group consisting of PTA-600, PTA-601, PTA-602 and PTA-603, all on deposit with the American Type Culture Collection.
In further embodiments of the present invention, the vaccines described above use an
H. somnus
genetically engineered to express one or more protective antigens. In further embodiments, the protective antigens are from bacterial pathogens other than
H. somnus.
Other objects, features and advantages of the present invention will become apparent from the following detailed description.


REFERENCES:
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Yang et al., “Apoptosis: A possible tactic ofHaemophilus somnusfor evasion of killing by bovine neutrophils?”Microbiol Pathogenesis, 24:351-159, (1998).

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