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Infect Immun. 1996 October; 64(10): 4074–4077.
PMCID: PMC174339

Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.

Abstract

The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of Shigella sonnei and Shigella flexneri type 2a covalently bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% of S. sonnei-rEPA recipients and 73 to 77% of S. flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years, these remained higher than at prevaccination (P < 0.01). There was a fourfold or greater increase in IgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG was the highest and most sustained class of LPS antibodies. Reinjection at day 42 did not boost antibody levels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA. had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA, respectively. On the basis of these data, further evaluation of the Shigella conjugates for protective efficacy in field trials in Israel was started.

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Selected References

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  • Ashkenazi S, May-Zahav M, Dinari G, Gabbay U, Zilberberg R, Samra Z. Recent trends in the epidemiology of Shigella species in Israel. Clin Infect Dis. 1993 Nov;17(5):897–899. [PubMed]
  • Chu CY, Liu BK, Watson D, Szu SS, Bryla D, Shiloach J, Schneerson R, Robbins JB. Preparation, characterization, and immunogenicity of conjugates composed of the O-specific polysaccharide of Shigella dysenteriae type 1 (Shiga's bacillus) bound to tetanus toxoid. Infect Immun. 1991 Dec;59(12):4450–4458. [PMC free article] [PubMed]
  • Cohen D, Block C, Green MS, Lowell G, Ofek I. Immunoglobulin M, A, and G antibody response to lipopolysaccharide O antigen in symptomatic and asymptomatic Shigella infections. J Clin Microbiol. 1989 Jan;27(1):162–167. [PMC free article] [PubMed]
  • Cohen D, Green M, Block C, Slepon R, Ambar R, Wasserman SS, Levine MM. Reduction of transmission of shigellosis by control of houseflies (Musca domestica) Lancet. 1991 Apr 27;337(8748):993–997. [PubMed]
  • Cohen D, Green MS, Block C, Rouach T, Ofek I. Serum antibodies to lipopolysaccharide and natural immunity to shigellosis in an Israeli military population. J Infect Dis. 1988 May;157(5):1068–1071. [PubMed]
  • Cohen D, Green MS, Block C, Slepon R, Ofek I. Prospective study of the association between serum antibodies to lipopolysaccharide O antigen and the attack rate of shigellosis. J Clin Microbiol. 1991 Feb;29(2):386–389. [PMC free article] [PubMed]
  • Cryz SJ, Jr, Sadoff JC, Fürer E. Immunization with a Pseudomonas aeruginosa immunotype 5 O polysaccharide-toxin A conjugate vaccine: effect of a booster dose on antibody levels in humans. Infect Immun. 1988 Jul;56(7):1829–1830. [PMC free article] [PubMed]
  • DuPont HL, Hornick RB, Dawkins AT, Snyder MJ, Formal SB. The response of man to virulent Shigella flexneri 2a. J Infect Dis. 1969 Mar;119(3):296–299. [PubMed]
  • DuPont HL, Levine MM, Hornick RB, Formal SB. Inoculum size in shigellosis and implications for expected mode of transmission. J Infect Dis. 1989 Jun;159(6):1126–1128. [PubMed]
  • Ekwall E, Haeggmann S, Kalin M, Svenungsson B, Lindberg AA. Antibody response to Shigella sonnei infection determined by an enzyme-linked immunosorbent assay. Eur J Clin Microbiol. 1983 Jun;2(3):200–205. [PubMed]
  • Granoff DM, Shackelford PG, Pandey JP, Boies EG. Antibody responses to Haemophilus influenzae type b polysaccharide vaccine in relation to Km(1) and G2m(23) immunoglobulin allotypes. J Infect Dis. 1986 Aug;154(2):257–264. [PubMed]
  • Green MS, Block C, Cohen D, Slater PE. Four decades of shigellosis in Israel: epidemiology of a growing public health problem. Rev Infect Dis. 1991 Mar-Apr;13(2):248–253. [PubMed]
  • Green MS, Cohen D, Block C, Rouach Z, Dycian R. A prospective epidemiologic study of shigellosis in the Israel Defense Forces: implications for the use of shigella vaccines. Isr J Med Sci. 1987 Jul;23(7):811–815. [PubMed]
  • Henry FJ, Alam N, Aziz KM, Rahaman MM. Dysentery, not watery diarrhoea, is associated with stunting in Bangladeshi children. Hum Nutr Clin Nutr. 1987 Jul;41(4):243–249. [PubMed]
  • Herrington DA, Van de Verg L, Formal SB, Hale TL, Tall BD, Cryz SJ, Tramont EC, Levine MM. Studies in volunteers to evaluate candidate Shigella vaccines: further experience with a bivalent Salmonella typhi-Shigella sonnei vaccine and protection conferred by previous Shigella sonnei disease. Vaccine. 1990 Aug;8(4):353–357. [PubMed]
  • Lue C, Prince SJ, Fattom A, Schneerson R, Robbins JB, Mestecky J. Antibody-secreting peripheral blood lymphocytes induced by immunization with a conjugate consisting of Streptococcus pneumoniae type 12F polysaccharide and diphtheria toxoid. Infect Immun. 1990 Aug;58(8):2547–2554. [PMC free article] [PubMed]
  • Miller MA, Meschievitz CK, Ballanco GA, Daum RS. Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period. Pediatrics. 1995 Apr;95(4):522–527. [PubMed]
  • Orr N, Robin G, Lowell G, Cohen D. Presence of specific immunoglobulin A-secreting cells in peripheral blood after natural infection with Shigella sonnei. J Clin Microbiol. 1992 Aug;30(8):2165–2168. [PMC free article] [PubMed]
  • Robbins JB, Chu C, Schneerson R. Hypothesis for vaccine development: protective immunity to enteric diseases caused by nontyphoidal salmonellae and shigellae may be conferred by serum IgG antibodies to the O-specific polysaccharide of their lipopolysaccharides. Clin Infect Dis. 1992 Aug;15(2):346–361. [PubMed]
  • Robbins JB, Schneerson R. Polysaccharide-protein conjugates: a new generation of vaccines. J Infect Dis. 1990 May;161(5):821–832. [PubMed]
  • Schneerson R, Robbins JB, Parke JC, Jr, Bell C, Schlesselman JJ, Sutton A, Wang Z, Schiffman G, Karpas A, Shiloach J. Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates. Infect Immun. 1986 May;52(2):519–528. [PMC free article] [PubMed]
  • Smollan G, Block C. Development of antimicrobial drug resistance among Shigellas isolated at an Israeli hospital from 1977 through 1990. Public Health Rev. 1990;18(4):319–327. [PubMed]
  • Taylor DN, Echeverria P, Pál T, Sethabutr O, Saiborisuth S, Sricharmorn S, Rowe B, Cross J. The role of Shigella spp., enteroinvasive Escherichia coli, and other enteropathogens as causes of childhood dysentery in Thailand. J Infect Dis. 1986 Jun;153(6):1132–1138. [PubMed]
  • Taylor DN, Trofa AC, Sadoff J, Chu C, Bryla D, Shiloach J, Cohen D, Ashkenazi S, Lerman Y, Egan W, et al. Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids. Infect Immun. 1993 Sep;61(9):3678–3687. [PMC free article] [PubMed]

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