Capsular polysaccharide-protein conjugate vaccines of carbotype 1 Vibrio vulnificus: construction, immunogenicity, and protective efficacy in a murine model.

S J Devi, U Hayat, C E Frasch, A S Kreger, J G Morris
Author Information
  1. S J Devi: Division of Bacterial Products, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA.

Abstract

Vibrio vulnificus causes septicemia and wound infections in immunocompromised humans. The capsular polysaccharide of Vibrio vulnificus (VvPS) is critical for virulence. We synthesized conjugate vaccines of carbotype 1 VvPS under conditions and in formulations suitable for human use. Purified VvPS was conjugated to tetanus toxoid (TT) or to inactivated V. vulnificus cytolysin or elastase by two different schemes. All conjugates elicited elevated anticapsular immunoglobulin G (IgG) and IgM and antiprotein IgG responses in mice compared with saline placebo. The conjugates prepared through caboxyl activation of VvPS (VvPS-TTa, VvPS-cytolysin, and VvPS-elastase) were more immunogenic than the one prepared through hydroxyl activation (VvPS-TTb). The protective efficacy of conjugated and unconjugated formulations of VvPS and that of protein carriers were evaluated in a mouse septicemia model. Eighty percent of mice actively immunized with VvPS-TTa vaccine survived challenge with carbotype 1 V. vulnificus, while VvPS-cytolysin and VvPS-elastase conjugates conferred 44 and 40% protection, respectively. Control mice immunized with VvPS, cytolysin, or elastase alone, or saline only, showed 70 to 100% mortality. VvPS-TTa vaccine is nontoxic, immunogenic, and protective in mice.

References

  1. Ann Intern Med. 1988 Aug 15;109(4):261-3 [PMID: 3293491]
  2. J Gen Microbiol. 1987 Jul;133(7):1783-91 [PMID: 3312481]
  3. J Infect Dis. 1989 Dec;160(6):985-93 [PMID: 2584765]
  4. Infect Immun. 1990 Jun;58(6):1769-73 [PMID: 2160432]
  5. Infect Immun. 1991 Jan;59(1):192-7 [PMID: 1846124]
  6. J Am Acad Dermatol. 1991 Mar;24(3):397-403 [PMID: 2061435]
  7. Infect Immun. 1991 Oct;59(10):3700-7 [PMID: 1716613]
  8. West J Med. 1991 Oct;155(4):400-3 [PMID: 1771878]
  9. J Bacteriol. 1992 Apr;174(8):2620-30 [PMID: 1556081]
  10. Infect Immun. 1992 May;60(5):2128-32 [PMID: 1373407]
  11. JAMA. 1993 Jan 13;269(2):246-8 [PMID: 8417244]
  12. J Infect Dis. 1993 Sep;168(3):758-62 [PMID: 8354917]
  13. Science. 1993 Oct 15;262(5132):416-9 [PMID: 8211161]
  14. Infect Immun. 1994 Aug;62(8):3590-3 [PMID: 8039936]
  15. J Clin Invest. 1994 Jul;94(1):286-92 [PMID: 7518832]
  16. Vaccine. 1994 Aug;12(10):875-8 [PMID: 7975828]
  17. Clin Microbiol Rev. 1995 Jan;8(1):48-86 [PMID: 7704895]
  18. J Exp Med. 1969 Jun 1;129(6):1367-84 [PMID: 4977283]
  19. N Engl J Med. 1979 Jan 4;300(1):1-5 [PMID: 758155]
  20. Trans R Soc Trop Med Hyg. 1979;73(1):3-9 [PMID: 442179]
  21. Lancet. 1979 Oct 27;2(8148):903 [PMID: 90993]
  22. Infect Immun. 1981 May;32(2):964-6 [PMID: 6788703]
  23. Infect Immun. 1981 Aug;33(2):583-90 [PMID: 7024134]
  24. J Infect Dis. 1981 Sep;144(3):244-8 [PMID: 7276636]
  25. J Infect Dis. 1984 Apr;149(4):558-61 [PMID: 6725989]
  26. Infect Immun. 1984 Sep;45(3):537-43 [PMID: 6469346]
  27. J Infect Dis. 1984 Sep;150(3):413-8 [PMID: 6481186]
  28. Infect Immun. 1985 Feb;47(2):446-51 [PMID: 2578434]
  29. N Engl J Med. 1985 Feb 7;312(6):343-50 [PMID: 3881668]
  30. Infect Immun. 1985 Apr;48(1):62-72 [PMID: 3980095]
  31. JAMA. 1985 May 17;253(19):2850-3 [PMID: 3989959]
  32. Infect Immun. 1985 Nov;50(2):534-40 [PMID: 3902648]
  33. Infect Immun. 1985 Dec;50(3):922-4 [PMID: 4066036]
  34. Infect Immun. 1986 Mar;51(3):964-5 [PMID: 3949387]
  35. Infect Immun. 1987 Jan;55(1):269-72 [PMID: 2432016]
  36. J Infect Dis. 1987 Feb;155(2):236-41 [PMID: 3805762]
  37. Gastroenterology. 1987 Mar;92(3):796-9 [PMID: 3817400]
  38. Microbiol Immunol. 1987;31(5):393-401 [PMID: 3116370]
  39. Ann Intern Med. 1988 Aug 15;109(4):318-23 [PMID: 3260760]

MeSH Term

Animals
Antibodies, Bacterial
Antigens, Bacterial
Bacterial Capsules
Bacterial Proteins
Bacterial Vaccines
Female
Mice
Sepsis
Vibrio
Vibrio Infections

Chemicals

Antibodies, Bacterial
Antigens, Bacterial
Bacterial Proteins
Bacterial Vaccines

Word Cloud

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