Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant or stably-transformed bacterium encoding one or...
Patent
1995-01-05
1999-02-23
Caputa, Anthony C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant or stably-transformed bacterium encoding one or...
4242611, 4242351, 4242031, 4352521, 4352523, 435243, 435 693, 435909, A61K 39106, C12N 121
Patent
active
058740880
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The field of invention is Vibrio cholerae vaccines. After more than 100 years of research on cholera, there remains a need for an effective cholera vaccine. There have been six pandemics of this disease caused by strains of V. cholera belonging to the "Classical" biotype. The etiological agents of the current (seventh) pandemic belong to the "El Tor" biotype (Finkelstein, Crit. Rev. Microbiol 2:553-623, 1973, Wachsmuth et al., The Lancet 337:1097-1098, 1991). Recently the seventh pandemic has extended to a new locale, that of South America. Beginning in January of 1991, an epidemic of cholera resulted in greater than 250,000 cases and over 2,000 deaths in Peru, Ecuador, Columbia, and Chile. Before this epidemic it was estimated that over 200,000 cases of cholera occurred per year mainly in India, Bangladesh, Africa and Western Asia (Tacket et al., Cholera Vaccines. In Vaccines: New Approaches to Immunological Problems, Ellis, R. W., editor, Butterworth-Heinemann, Boston, 1992).
In November of 1992, an antigenically distinct, non-01 form of V. cholerae emerged in India and Bangladesh and within eight months caused an estimated 500,000 cases and 6,000 deaths. The pandemic potential of this new strain, designated serogroup 0139 synonym "Bengal", seems assured and is a new cause of concern throughout the developing world. These recent experiences underline the need for effective cholera vaccines against disease due to both El Tor 01 and Bengal 0139 serotypes of V. cholerae.
Because natural infection by and recovery from cholera induces immunity lasting at least 3 years (Tacket et al., Supra; Levine et al., J. Infect. Dis. 143:818-820, 1981; Cash et al., J. Infect. Dis. 130:325-333, 1974), much effort has been made to produce live, attenuated cholera vaccines that when administered orally would mimic the disease in its immunization properties but would not cause adverse symptoms or reactions in the immunized individual (i.e., display low reactogenicity). Vaccines of this type involve deletion mutations that inactivate the gene encoding the A subunit of cholera toxin, a protein which is responsible for most of the diarrhea seen in this disease (Mekalanos et al., Proc. Natl. Acad. Sci. U.S.A. 79:151-155, 1982; Mekalanos et al., Nature 306:551-557, 1983; Kaper et al., Nature 308:655-658, 1984; Kaper et al., Biotechnology 2:345, 1984; Pierce et al., Infect. Immun. 55:477-481, 1987; Taylor et al., Vaccine 6:151-154, 1988; Levine et al., Infn. Immun. 56:161-167, 1988; Herrington et al. J. Exper. Med. 168:1487-1492, 1988; Levine et al., Lancet ii:467-470, 1988; Kaper et al., Res. Microbiol. 141:901-906, 1990; Pearson et al., Res. Microbiol. 141:893-899, 1990). See also Mekalanos, U.S. Pat. Nos. 5,098,998 and 4,882,278, and Kaper et al., U.S. Pat. No. 4,935,364, hereby incorporated by reference. While both oral, killed whole cell vaccines and several live, attenuated cholera vaccine have been developed, the most promising of these provide little protection against the El Tor biotype of V. cholerae and probably no protection against the 0139 serotype. The major issues associated with cholera vaccines are safety, stability and their degree of antigenicity.
With regard to the toxin genes of V. cholerae, the genetic diversity among toxigenic and non-toxigenic strains has been examined by Chen et al. (1991, Epidemiol. Infect. 107:225). Mekalanos (1983, Cell 35:253) reports on the duplication and amplification of V. cholerae toxin genes, and Miller et al. (1984, Proc. Natl. Acad. Sci. U.S.A. 81:3471) discusses transcriptional regulation of the toxin genes. Other V. cholerae genes whose products may play a role in the pathogenicity of this organism include the toxin-coregulated pilus genes (Shaw et al., 1990, Infect. Immun. 58:3042; Sharma et al., 1989, Vaccine, 7:451; Sun et al., 1990, J. Infect. Dis. 161:1231; Hall et al., 1991, Infect. Immun. 59:2508; Taylor et al., 1987, Proc. Natl. Acad. Sci. U.S.A. 84:2833), and the gene encoding the intestinal colonalization factor (Taylor et al., 1988, Vac
REFERENCES:
patent: 4882278 (1989-11-01), Mekalanos
patent: 4935364 (1990-06-01), Kaper et al.
patent: 5098998 (1992-03-01), Mekalanos et al.
Pinkerton et al. Science 262:160-162, Oct. 1993.
Gregory D. Pearson et al. CTX Genetic Element Encodes a Site-Specific Recombination System and an Intestinal Colonization Factor, Proc. Natl. Acad. Sci. USA, vol. 90, 3750-3754, 1993.
Kathleen Richardson et al. "Transposon-Induced non-motile mutants of Vibrio Cholerae" Journal of General Microbiology, vol. 136, 717-725, 1990.
Cash et al., "Response of Man to Infection with Vibrio cholerae, II, Protection from Illness Afforded by Previous Disease and Vaccine", Journal of Infectious Diseases 130:325-333, 1974.
Finkelstein, "Cholera", Critical Reviews in Microbiology 2:553-623, 1973.
Freter et al., "Adhesive Properties of Vibrio cholerae: Nature of the Interaction With Intact Mucosal Surfaces" Infection and Immunity 14:246-256, 1976.
Freter et al., "Role of Chemotaxis in the Association of Motile Bacteria With Intestinal Mucosa: Fitness and Virulence of Nonchemotactic Vibrio cholerae Mutants in Infant Mice" Infection and Immunity 34:222-233, 1981.
Freter et al., "Role of Chemotaxis in the Association of Motile Bacteria with Intestinal Mucosa: In Vivo Studies" Infection and Immunity 34:234-240, 1981.
Guentzel et al., "Motility as a Virulence Factor for Vibrio cholerae" Infection and Immunity 11:890-897, 1975.
Herrington et al., "Toxin, Toxin-coregulated Pili, and the toxR Regulon are Essential for Vibrio Cholerae Pathogenesis in Humans", J. Experimental Medicine 168:1487-1492, 1988.
Jones et al., "Adhesive Properties of Vibrio cholerae: Adhesion to Isolated Rabbit Brush Border Membranes and Hemagglutinating Activity" Infection and Immunity 14:232-239, 1976.
Jones et al., "Adhesive Properties of Vibrio cholerae: Nature of the Interaction With Isolated Rabbit Brush Border Membranes and Human Erythrocytes", Infection and Immunity 14:240-245, 1976.
Kaper et al., "A Recombinant Live Oral Cholera Vaccine", Biotechnology, Apr. 1984, pp. 345-349.
Kaper et al., "Recombinant nontoxinogenic Vibrio cholerae strains as attenuated cholera vaccine candidates" Nature 308:655-658, 1984.
Levine et al., "Duration of Infection-Derived Immunity to Cholera", J. Infectious Diseases 143:818-820, 1981.
Levine et al., "The Pathogenicity of Nonenterotoxigenic Vibrio cholerae Serogroup 01 Biotype El Tor Isolated from Sewage Water in Brazil", J. Infectious Diseases 145:296-299, 1982.
Levine et al., "Volunteer Studies of Deletion Mutants of Vibrio cholerae 01 Prepared by Recombinant Techniques" Infection and Immunity 56:161-167, 1988.
Levine et al., "Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 102 and CVD 103-HgR", The Lancet II:467-470, 1988.
Mekalanos, "Duplication and Amplification of Toxin Genes in Vibrio cholerae", Cell 35:253-263, 1983.
Mekalanos et al., "Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development", Nature 306:551-557, 1983.
Mekalanos et al., "Isolation of enterotoxin structural gene deletion mutations in Vibrio cholerae induced by two mutagenic vibriophages" PNAS USA 79:151-155, 1982.
Mostow et al., "High-Frequency Spontaneous Mutation of Classical Vibrio cholerae to a Nonmotile Phenotype", Infection and Immunity 58:3633-3639, 1990.
Pearson et al., "New Attenuated Derivatives of Vibrio cholerae", Res. Microbiol. 141:893-899, 1990.
Pierce et al., "Determinants of the Immunogenicity of Live Virulen and Mutant Vibrio cholerae 01 in Rabbit Intestine", Infection and Immunity 55:477-481, 1987.
Richardson, "Roles of motility and flagellar structure in pathogenicity of Vibrio cholerae: Analysis of motility mutants in three animal models", Infection and Immunity 59:2727-2736, 1991.
Richardson et al., Transposon-induced non-motile mutants of Vibrio cholerae, J. General Microbiology 136:717-725, 1990.
Taylor et al., "Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin", PN
Bieker-Brady K.
Caputa Anthony C.
President and Fellows of Harvard College
LandOfFree
Deletion mutants of cholera vaccines expressing heterologous ant does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Deletion mutants of cholera vaccines expressing heterologous ant, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Deletion mutants of cholera vaccines expressing heterologous ant will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-304214