Shigella infeksiyonlarında koruyucu așı çalıșmaları

Enterobacteriaceae ailesinin bir üyesi olan Shigella cinsi tüm dünyada endemik olarak görülmekte, özellikle gelișmekte olan ülkelerde yüksek mortalite ile seyreden infeksiyonlara neden olmaktadır. Hastalık çoğunlukla 5 yașın altındaki çocuklarda görülmekte ve dünyada çocuk ölümü nedenlerinin arasında önemli bir yer tutmaktadır. Dünya Sağlık Örgütü (WHO) șigelloza karșı koruyucu așı geliștirme çalıșmalarını öncelikleri arasına almıștır. Shigella infeksiyonları için koruyucu așılar, bakteri O polisakkariti tașıyıcı bir protein ile bağlanarak parenteral, oral veya intranazal uygulanan konjuge așılar; hastalık olușturmadan koruyucu etki sağlamayı hedefleyen canlı attenue așılar; patogenezde rol oynayan genlerin aydınlatılması ile genetik yoldan elde edilecek canlı oral așılar; hibrit canlı vektör Shigella așıları; geniș spektrumlu așılar ve invazin kompleks așısı üzerinde yoğunlașmıștır. Son yıllarda Shigella virülans faktörlerinin ve patogenezinin iyice aydınlatılması ile gelecekte umut vaad eden așılar elde edilmiștir. Bu derlemede, koruyucu ve güvenilir așı elde etmek için geçmișten günümüze yapılan așı geliștirme stratejileri incelenmiștir.

Protective vaccine researches in Shigella İnfections

Shigella, a member of enterobacteriaceae, is endemic over the world and causes infections with high mortality rates especially in developing countries. Disease is more common among children under 5 years old and is an important cause of children death in world. World health organisation (WHO) consider the researches of a protective vaccine developement for shigellosis as a priority. Protective vaccines for Shigella infections are focused on conjugate vaccines based on bacterial O polysaccharide linked to a carrier protein administered by parenteral, oral or intranasal; live attenued vaccines conferring protection without causing disease; live oral vaccines obtained by genetic process following the discover of genes involved in pathogenesis; hybrid live vector Shigella vaccines; wide spectrum vaccines and invazincomplex vaccines. Last years, since virulance factors and pathogenesis of Shigella are discovered, promising vaccines for future are developed. In this review, vaccine developement strategies for obtaining protective and safe vaccines from past to now are investigated.

PDF

___

Dupont, HL. Shigella Species (Bacillary Dysentery). In: Mandell GL, Bennett JE, editors. Mandell, Douglas, and Bennetts Principles and Practice of Infectious Diseases. Philadelphia: Churchill Livingstone Elsevier.; 2010. p. 2905-2919.
Aysev AD. Shigella Türleri. In: Topçu AW, Söyletir G, Doğanay M, editors. İnfeksiyon Hastalıkları ve Mikrobiyolojisi, Etkenlere Göre İnfeksiyonlar. İstanbul: Nobel Tıp Kitapevleri.; 2008. p. 2164- 2168.
Butler T, Scheld WM. Shigellosis. In: Goldman L, Ausiello D, editors. Cecil Textbook of Medicine. Philadelphia: Saunders.; 2004. p. 1852-1854.
Erdem B. Enterobacteriaceae. In: Mutlu G, İzmir T, Cengiz AT, Ustaçelebi Ş, Tümbay E, Mete Ö editors. Temel ve Klinik Mikrobiyoloji. Ankara: Güneş Kitabevi.; 1999. p. 471-515.
Black RE, Lanata CF. Diarrheal Diseases. In: Nelson KE, Williams CFM, editors. Infectious Disease Epidemiology: Theory and Practice. Massachusetts: Jones and Bartlett Publishers.; 2007. p. 759-786.
Levine MM, Kotloff KL, Barry EM, et al. Clinical Trials of Shigella Vaccines: Two Steps forward and One Step Back On a Long, Hard Road. Nat Rev Microbiol 2007;5(7): 540553.
Ferreccio C, Prado V, Ojeda A, et al. Epidemiologic patterns of acute diarrhea and endemic Shigella infections in a poor periurban setting in Santiago, Chile. Am. J. Epidemiol 1991;134: 614627.
Tacket CO, Binion SB, Bostwick E, et al. Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Am. J. Trop. Med. Hyg 1992;47: 276-283.
Kaminski RW, Oaks EV. Inactivated and subunit vaccines to prevent shigellosis. Expert Rev Vaccines 2009;8(12): 1693- 1704.
Cohen D, Ashkenazi S, Green M, et al. Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers. Infect Immun 1996;64: 40744077.
Cohen D, Ashkenazi S, Green MS, et al. Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults. Lancet 1997;349(9046): 155-159.
Ashkenazi S, Passwell JH, Harlev E, et al. Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children. J Infect Dis 1999;179(6): 1565-1568.
Passwell JH, Ashkenazi S, Harlev E, et al. Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2arEPAsucc conjugate vaccines in 14- yearold children. Pediatr Infect Dis J 2003;22(8): 701706.
Chowers, Y., Kirschner, J., Keller, et al. O-Specific polysaccharide conjugate vaccine-induced IgG antibodies prevent invasion of Shigella into Caco-2 cells and may be curative. Proc. Natl. Acad. Sci 2007;104: 2396-2401.
http://clinicaltrials.gov/archive/NCT003683 16/2010_01_28 tarih: 2010_01_28 )
Orr N, Robin G, Cohen D, et al. Immunogenicity and efficacy of oral or intranasal Shigella flexneri 2a and Shigella sonnei proteosome-lipopolysaccharide vaccines in animal models. Infect Immun 1993;61(6): 2390-2395.
Orr N, Arnon R, Rubin G, et al. Enhancement of anti-Shigella lipopolysaccharide (LPS) response by addition of the cholera toxin B subunit to oral and intranasal proteosome-Shigella flexneri 2a LPS vaccines. Infect Immun 1994;62(11): 5198-5200.
Fries LF, Montemarano AD, Mallett CP, et al. Safety and immunogenicity of a proteosome-Shigella flexneri 2a lipopolysaccharide vaccine administered intranasally to healthy adults. Infect Immun 2001;69(7): 4545-4553.
Levenson VI, Chernokhvostova EV, Lyubinskaya MM, et al. Parenteral immunization with Shigella ribosomal vaccine elicits local IgA response and primes for mucosal memory. Int Arch Allergy Appl Immunol 1988;87(1): 25-31.
Shima DH, Changa SY, Park SM, et al. Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from Shigella flexneri 2a. Vaccine 2007;25: 48284836.
Phalipon A, Costachel C, Grandjean C, et al. Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine. J Immunol 2006;176(3): 1686-1694.
Mel DM., Papo RG., Terzin AL, et al. Studies on vaccination against bacillary dysentery. 2. Safety tests and reactogenicity studies on a live dysentery vaccine intended for use in field trials. Bull. World Health Organ 1965;32: 637645.
Mel DM, Arsic BL, Nikolic BD, et al. Studies on vaccination against bacillary dysentery. 4. Oral immunization with live monotypic and combined vaccines. Bull. World Health Organ 1968;39: 375380.
Mel DM, Gangarosa EJ, Radovanovic ML, et al. Studies on vaccination against bacillary dysentery. 6. Protection of children by oral immunization with streptomycin-dependent Shigella strains. Bull. World Health Organ 1971;45: 457 464.
Kweon MN. Shigellosis: The Current Status of Vaccine Development. Curr Opin Infect Dis 2008;21: 313318.
Bingrui W. Study on the effect of oral immunization of T32-Istrati strain against bacillary dysentery in field trials. Arch. Roum. Pathol. Exp. Microbiol 1984;43: 285289.
Phalipon A, Sansonetti PJ. Shigellosis: innate mechanisms of inflammatory destruction of the intestinal epithelium, adaptive immune response, and vaccine development. Crit Rev Immunol 2003;23(5-6): 371-401.
Coster TS, Hoge CW, VanDeVerg LL, et al. Vaccination against shigellosis with attenuated Shigella flexneri 2a strain SC602. Infect Immun 1999;67(7): 3437-3443.
Launay O, Sadorge C, Jolly N, et al. Safety and immunogenicity of SC599, an oral live attenuated Shigella dysenteriae type-1 vaccine in healthy volunteers: results of a Phase 2, randomized, double-blind placebo-controlled trial. Vaccine 2009;27(8): 1184-1191.
Kotloff KL, Noriega F, Losonsky GA, et al. Safety, immunogenicity, and transmissibility in humans of CVD 1203, a live oral Shigella flexneri 2a vaccine candidate attenuated by deletions in aroA and virG. Infect Immun 1996;64(11): 4542-4548.
Kotloff KL, Noriega FR, Samandari T, et al. Shigella flexneri 2a strain CVD 1207, with specific deletions in virG, sen, set, and guaBA, is highly attenuated in humans. Infect Immun 2000;68(3): 1034- 1039.
Kotloff KL, Pasetti MF, Barry EM, et al. Deletion in the Shigella enterotoxin genes further attenuates Shigella flexneri 2a bearing guanine auxotrophy in a phase 1 trial of CVD 1204 and CVD 1208. J Infect Dis 2004;190(10): 1745-1754.
Kotloff KL, Taylor DN, Sztein MB, et al. Phase I evaluation of delta virG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults. Infect Immun 2002;70(4): 2016-2021.
Venkatesan MM, Hartman AB, Newland JW, et al. Construction, characterization, and animal testing of WRSd1, a Shigella dysenteriae 1 vaccine. Infect Immun 2002;70(6): 2950-2958.
Ranallo RT, Thakkar S, Chen Q, et al. Immunogenicity and characterization of WRSF2G11: A second generation live attenuated Shigella flexneri 2a vaccine strain. Vaccine 2007;25: 22692278.
Formal SB, Baron LS, Kopecko DJ, et al. Construction of a potential bivalent vaccine strain: introduction of Shigella sonnei form I antigen genes into the galE Salmonella typhi Ty21a typhoid vaccine strain. Infect Immun 1981;34(3): 746-750.
Levine MM, Woodward WE, Formal SB, et al. Studies with a new generation of oral attenuated Shigella vaccine: Escherichia coli bearing surface antigens of Shigella flexneri. J Infect Dis 1977;136(4): 577-582. Kotloff KL, Herrington DA, Hale TL, et al. Safety, immunogenicity, and efficacy in monkeys and humans of invasive Escherichia coli K-12 hybrid vaccine candidates expressing Shigella flexneri 2a somatic antigen. Infect Immun 1992;60(6): 2218-2224.
Newland JW, Hale TL, Formal, SB. Genotypic and phenotypic characterization of an aroD deletionattenuated Escherichia coli K12Shigella flexneri hybrid vaccine expressing S. flexneri 2a somatic antigen. Vaccine 1992;10: 766776.
Kotloff KL, Losonsky GA, Nataro JP, et al. Evaluation of the safety, immunogenicity, and efficacy in healthy adults of four doses of live oral hybrid Escherichia coli- Shigella flexneri 2a vaccine strain EcSf2a-2. Vaccine 1995;13(5): 495-502.
Noriega FR, Liao FM, Maneval DR, et al. Strategy for cross-protection among Shigella flexneri serotypes. Infect Immun 1999;67(2): 782-788.
Oaks EV, Turbyfill KR. Development and evaluation of a S. flexneri 2a and S. sonnei bivalent invasin complex (Invaplex) vaccine. Vaccine 2006;24(13): 2290-2301