Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Conjugate or complex
Patent
1992-08-21
1995-08-29
Nucker, Christine M.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Conjugate or complex
42419711, 4242441, 4242401, 424831, 530402, 530403, A61K 39385, A61K 3909, A61K 3910
Patent
active
054458170
ABSTRACT:
A medically important and useful conjugate comprising pertussis toxin (PT), or another antigen having similar physico-chemical properties, as the carrier protein component, coupled to a neutral or non-charged saccharide, particularly, the capsular polysaccharide of Streptococcus pneumoniae type 14 (Pn14), for use as an effective, non-toxic, and highly immunogenic vaccine is described. The invention is directed to a novel synthetic scheme wherein PT and like proteins, and a derivative of Pn14, and the like, were coupled at acidic pH via carbodiimide-mediated condensation to produce an immunogenic conjugate. The coupling procedure yielded a Pn14-PT conjugate in which the PT component was rendered non-toxic and both the PT and Pn14 components were immunogenic, as determined by the production of protective levels of both type-specific and neutralizing antibodies in mammals. The Pn14-PT conjugate was used as an immunogen at levels estimated to be protective in humans and stands to provide an effective, safe, and potent human vaccine.
REFERENCES:
patent: 4693891 (1987-09-01), Collins et al.
patent: 4774086 (1988-09-01), Quentin-Miller et al.
patent: 4784589 (1988-11-01), Robinson et al.
patent: 4788058 (1988-11-01), Parton et al.
patent: 5045203 (1991-09-01), Quentin-Miller et al.
patent: 5153312 (1992-10-01), Porro
Kallings et al, Lancet I: 955-960, 1988.
Schneerson, R., et al, Infection and Immunbity 52(2):519-528, 1986.
Sekura, R D, et al, Pertussis Toxin: Affinity Purification of a New ADP-Ribosyltransferase J. Biol Chem 23(2):14647-14651, 1983.
Robbins, J B, et al, Journal of Infectious Diseases 148(6):1136-1159, 1983.
Bauminger S, et al, Methods in Enzymology 70:151-159, 1980.
R. Schneerson, et al., 1984. "Serum Antibody Responses of Juvenile and Infant Rhesus Monkeys Injected with Haemophilus influenzae Type b and Pneumococcus Type 6A Capsular Polysaccharide-Protein Conjugates". Infect. and Immun., 45(3):582-591.
Schreurs, A. J. M. et al., 1983, "Bacterial cell wall components decrease the number of guinea pig lung beta-adrenoceptors." Chem. Abstrs., 98(15), Abstract No. 123740x, 11 Apr. 1983.
P. Anderson et al., 1989, "Human adult immunogeniciety of protein-coupled pneumococcal capsular antigens of serotypes prevalent in otitis media," Pediatr. Infect. Dis., 8:S50-S53.
A. F. M. Verheul et al., 1989, "Modulation of the immune response to pneumococcal type 14 capsular polysaccharide-protein conjugates by the adjuvant Quil A depends on the properties of the conjugates," Infect. Immun., 57:1078-1083.
J. H. M. Wigert et al., 1991, "Immunogenicity of Streptococcus pneumoniae type 14 capsular polysaccharide: Influence of carriers and adjuvants on isotype distribution," Infect. Immun., 59:2750-2757.
M. Porro et al., 1985, "A semisynthetic glycoconjugate antigen prepared by chemical glycosylation of pertussis toxin by a meningococcal group C polysaccharide oligosaccharide hapten". Proceedings of the Fourth International Symposium on Pertussis. Joint IABS/WHO.
J. B. Robbins et al., 1990, "Polysaccharide-protein conjugates: A new generation of vaccines," J. Infect. Dis., 161:821-832.
E. C. Beuvery et al., 1982, "Comparison of the induction of immunoglobulin M and G antibodies in mice with purified pneumococcal type 3 and meningococcal Group C polysaccharides and their protein conjugates," Infect. Immun., 37:15-22.
C. Y. Chu et al., 1983, "Further studies on the immunogenicity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugates," Infect. Immun., 40:245-256.
A. Fattom et al., 1990, "Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae Type 12F polysaccharide alone or conjugated to diphtheria toxoid," Infect. Immun., 58:2309-2312.
C. C. A. M. Peeters et al., 1991, "A comparative study of the immunogenicity of pneumococcal Type 4 polysaccharide and oligosaccharide tetanus toxoid conjugates in adult mice," J. Immunol., 146:4308-4314.
J. C. Paton et al., 1991, "Purification and immunogenicity of genetically obtained pneumolysin toxoids and their conjugation to Streptococcus pneumoniae type 19F polysaccharide," Infect. Immun., 59:2297-2304.
M. Pittman, 1979, Pertussis toxin: "The cause of the harmful effects and prolonged immunity of whopping cough. A hypothesis," Rev. Infect. Dis., 1:401-412.
M. Pittman, 1975, "Determination of the histamine sensitizing unitage of pertussis vaccine," J. Biol. Stand., 3:185-191.
M. Oda et al., 1984, "Protective activities of the filamentous-hemagglutinin and the lymphocytosis-promoting factor of Bordetella pertussis in mice," J. Infect. Dis., 150:823-833.
H. Sato et al., 1984, "Bordetella pertussis infection in mice: Correlation of specific antibodies against two antigens, pertussis toxin and filamentous hemagglutinin with mouse protectivity in intracerebral or aerosol challaenge system," Infect. Immun., 46:415-421.
P. Olin et al., 1989, "The efficacy of acellular pertussis vaccine," JAMA, 261:560.
R. D. Sekura et al., 1988, "Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide,"J. Pediatr., 113:806-813.
G. Zackrisson et al., "History of whooping cough in nonvaccinated Swedish children, related to serum antibodies to pertussis toxin and filamentous hemagglutinin," J. Pediatr., 116:190-194.
M. Granstrom et al., 1985, "Neutralizing antibodies to pertussis toxin in whooping cough," J. Infect. Dis., 151:646-649.
M. Granstrom et al., 1991, "Specific immunoglobulin for treatment of whopping cough," Lancet, 338:1230-1233.
R. Austrian et al., 1977, "The bacteriology of pneumococcal otitis media." John s Hopkins Medical J., 141:104-111.
J. M. Borgono et al., 1978, "Vaccination and revaccination with polyvalent pneumococcal polysaccharide vaccines in adults and infants," Proc. Soc. Exp. Biol. Med., 157:148-154.
E. Morch, 1943, "Serological studies on the Pneumococci," Eds. E. Munksgaard & H. Milford, Oxford University Press, p. 160.
P. H. Makela, 1980, "Pneumococcal vaccine and otitis media," Lancet, II:547-551.
J. B. Robbins et al., 1983, "Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-relative types within groups," J. Infect. Dis., 148:1136-1159.
G. Bolan et al., 1986, "Pneumococcal vaccine efficacy in selected populations in the United States," Ann. Int. Med., 104:1-6.
Levi Lily
Robbins John B.
Schneerson Rachel
Krsek-Staples Julie
Nucker Christine M.
The United States of America as represented by the Department of
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