Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Reexamination Certificate
1998-04-22
2002-06-25
Minnifield, Nita (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
C424S256100, C424S825000, C424S200100, C424S235100, C424S255100, C424S282100, C435S245000
Reexamination Certificate
active
06410021
ABSTRACT:
TECHNICAL FIELD
The invention relates to vaccines and in particular, live vaccines against
Actinobacillus pleuropneumoniae
(APP) and related bacterial pathogens. The invention is also concerned with recombinant techniques for preparing such a vaccine.
BACKGROUND OF THE INVENTION
An organism known as
Actinobacillus pleuropneumoniae
(APP) is a gram negative coccobacillus organism that is found in the pig and causes pneumonia in the pig.
This disease is characteristically an acute necrotizing hemorrhagic bronchopneumonia, with accompanying fibrinous pleuritis (Fenwick, B. and S. Henry. 1994. Porcine pleuropneumonia. J. Am. Vet. Med. Assoc. 204:1334-1340) (Sebunya, T. N. K. and J. R. Saunders. 1983.
Haemophilus pleuropneumoniae
infection in swine: a review. J. Am. Vet. Med. Assoc. 182:1331-1337). Porcine pleuropneumonia is an economically devastating, severe and often fatal disease with clinical courses ranging from hyperacute to chronic infection (Fenwick, B. and S. Henry. 1994. Porcine pleuropneumonia. J. Am. Vet. Med. Assoc. 204:1334-1340) (Hunneman, W. A. 1986. Incidence, economic effects, and control of
Haemophilus pleuropneumoniae
infections in pigs. Vet. Quarterly 8:83-87). The existence of at least twelve antigenically distinct capsular serotypes (Perry, M. B., E. Altman, J.-R. Brisson, L. M. Beynon, and J. C. Richards. 1990. Structural characteristics of the antigenic capsular polysaccharides and lipopolysaccharides involved in the serological classification of
Actinobacillus pleuropneumoniae
strains. Serodiag. Immunother. Infect. Dis. 4:299-308) has made development of a cross-protective vaccine difficult. Killed whole cell bacterins provide at best serotype-specific protection (Nielsen, R. 1984
. Haemophilus pleuropneumoniae
serotypes—Cross protection experiments. Nord. Vet. Med. 36:221-234) (Nielsen, R. 1976. Pleuropneumonia of swine caused by
Haemophilus pleuropneumoniae
. Studies on the protection obtained by vaccination. Nord. Vet. Med. 28:337-338) (Rosendal, S., D. S. Carpenter, W. R. Mitchell, and M. R. Wilson. 1981. Vaccination against pleuropneumonia in pigs caused by
Haemophilus pleuropneumoniae.
Can. Vet. J. 22:34-35) (Thacker, B. J., and M. H. Mulks. 1988. Evaluation of commercial
Haemophilus pleuropneumoniae
vaccines. Proc. Int. Pig Vet. Soc. 10:87). In contrast, natural or experimental infection with a highly virulent serotype of
A. pleuropneumoniae
elicits protection against reinfection with any serotype (Nielsen, R. 1979
. Haemophilus parahaemolyticus
serotypes: pathogenicity and cross immunity. Nord. Vet. Med. 31:407-413) (Nielsen, R. 1984
. Haemophilus pleuropneumoniae
serotypes—Cross protection experiments. Nord. Vet. Med. 36:221-234) (Nielsen, R. 1974. Serological and immunological studies of pleuropneumonia of swine caused by
Haemophilus parahaemolyticus.
Acta Vet. Scand. 15:80-89). In several recent studies, attenuated strains of
A. pleuropneumoniae
produced by chemical nutagenesis, serial passage, or other undefined spontaneous mutation have been tested as live vaccines, with promising results (Inzana, T. J., J. Todd, and H. P. Veit. 1993. Safety, stability and efficacy of nonencapsulated mutants of
Actinobacillus pleuropneumoniae
for use in live vaccines. Infect. Immun. 61:1682-1686) (Paltineanu, D., R. Pambucol, E. Tirziu, and I. Scobercea. 1992. Swine infectious pleuropneumonia: Aerosol vaccination with a live attenuated vaccine. Proc. Int. Pig. Vet. Soc. 12:214) (Utrera, V., C. Pijoan, and T. Molitor. 1992. Evaluation of the immunity induced in pigs after infection with a low virulence strain of
A. pleuropneumoniae
serotype 1. Proc. Int. Pig. Vet. Soc. 12:213). However, the use of live vaccines in the field is problematic, particularly when the attenuating lesion in the vaccine strain has not been genetically defined. A well-defined mutation that prevents reversion to wild-type would be extremely desirable for the development of a live attenuated vaccine against
Actinobacillus pleuropneumoniae.
A variety of mutations in biosynthetic pathways are known to be attenuating in other organisms. Lesions in aro(Hoiseth S. K. and B. A. D. Stocker. 1981. Aromatic-dependent
Salmonella typhimurium
are non-virulent and effective as live vaccines. Nature (london). 291: 238-239) (Homchampa, P., R. A. Strugnell and B. Adler. 1992. Molecular analysis of the aroA gene of
Pasteurella multocida
and vaccine potential of a constructed aroA mutant. Mol. Microbiol. 6: 3585-3593) (Homchampa, P., R. A. Strugnell and B. Adler. 1994. Construction and vaccine potential of an aroA mutant of
Pasteurella haemolytica.
Vet. Microbiol. 42:35-44) (Karnell, A., P. D. Cam, N. Verma and A. A. Lindberg. 1993. AroD deleteion attenuates
Shigella flexneri
strain 2457T and makes it a safe and efficacious oral vaccine in monkeys. Vaccine 8:830-836.) (Lindberg, A. A., A. Karnell, B. A. D. Stocker, S. Katakura, H. Sweiha and F. P. Reinholt. 1988. Development of an auxotrophic oral live
Shigella flexneri
vaccine. Vaccine 6:146-150) (O'Callaghan, D. D. Maskell, F. Y. Lieu, C. S. F. Easmon and G. Dougan. 1988. Characterization of aromatic and purine dependent
Salmonella typhimurium:
attenuation, persistence and ability to induce protective immunity in BALB/c mice. Infect. Immun. 56:419-423) (Vaughan, L. M., P. R. Smith, and T. J. Foster. 1993. An aromatic-dependent mutant of the fish pathogen
Aeromonas salmonicida
is attenuated in fish and is effective as a live vaccine against the Salmonid disease furunculosis. Infect. Immun. 61:2172-2181), pur (O'Callaghan, D. D. Maskell, F. Y. Lieu, C. S. F. Easmon and G. Dougan. 1988. Characterization of aromatic and purine dependent
Salmonella typhimurium:
attenuation, persistence and ability to induce protective immunity in BALB/c mice. Infect. Immun. 56:419-423) (Sigwart, D. F., B. A. D. Stocker, and J. D. Clements. 1989. Effect of a purA mutation on the efficacy of Salmonella live vaccine vectors. Infect. Immun. 57:1858-1861), and thy (Ahmed, Z. U., M. R. Sarker, and D. A. Sack. 1990. Protection of adult rabbits and monkeys from lethal shigellosis by oral immunization with a thymine-requiring and temperature-sensitive mutant of
Shigella flexneri
Y. Vaccine. 8:153-158) loci, which affect the biosynthesis of aromatic amino acids, purines, and thymine, respectively, are attenuating because they eliminate the ability of the bacterium to synthesize critical compounds that are not readily available within mammalian hosts. For example, aro mutants of Salmonella and Shigella species have been shown to be attenuated in their natural hosts (Hoiseth S. K. and B. A. D. Stocker. 1981. Aromatic-dependent
Salmonella typhimurium
are non-virulent and effective as live vaccines. Nature (london). 291: 238-239) (Homchampa, P., R. A. Strugnell and B. Adler. 1992. Molecular analysis of the aroA gene of
Pasteurella multocida
and vaccine potential of a constructed aroA mutant. Mol. Microbiol. 6: 3585-3593) (Homchampa, P., R. A. Strugnell and B. Adler. 1994. Construction and vaccine potential of an aroA mutant of
Pasteurella haemolytica.
Vet. Microbiol. 42:35-44) (Karnell, A., P. D. Cam, N. Verma and A. A. Lindberg. 1993. AroD deletion attenuates
Shigella flexneri
strain 2457T and makes it a safe and efficacious oral vaccine in monkeys. Vaccine 8:830-836) (Lindberg, A. A., A. Karnell, B. A. D. Stocker, S. Katakura, H. Sweiha and F. P. Reinholt. 1988. Development of an auxotrophic oral live
Shigella flexneri
vaccine. Vaccine 6:146-150) (O'Callaghan, D. D. Maskell, F. Y. Lieu, C. S. F. Easmon and G. Dougan. 1988. Characterization of aromatic and purine dependent
Salmonella typhimurium:
attenuation, persistence and ability to induce protective immunity in BALB/c mice. Infect. Immun. 56:419-423). Lesions that affect the biosynthesis of LPS (Collins, L. V., S. Attridge, and J. Hackett. 1991. Mutations at rfc or pmi attenuate
Salmonella typhimurium
virulence for mice. Infect. Immun. 59:1079-1085) (Nnalue, N. A., and B. A. D. Stocker. 1987. Tests of the virulence and live-vaccine efficacy of auxotrophic and
Fuller Troy E.
Mulks Martha H.
Thacker Bradley
LandOfFree
Vaccines of pasteurellaceae mutants and vaccination method does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vaccines of pasteurellaceae mutants and vaccination method, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vaccines of pasteurellaceae mutants and vaccination method will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2971008