Phase I Evaluation of Delta VirG Shigella Sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2002 Mar 16

PMID 11895966

Citations 43

Authors

Karen L Kotloff

David N Taylor

Marcelo B Sztein

Steven S Wasserman

Genevieve A Losonsky

James P Nataro

Malabi Venkatesan

Antoinette Hartman

William D Picking

David E Katz

James D Campbell

Myron M Levine

Thomas L Hale

Affiliations

Soon will be listed here.

Abstract

We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral Delta virG Shigella sonnei vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (n = 7) or vaccine (n = 27) at 3 x 10(3) CFU (group 1), 3 x 10(4) CFU (group 2), 3 x 10(5) CFU (group 3), or 3 x 10(6) CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients. WRSS1 was recovered from the stools of 50 to 100% of the vaccinees in each group. The geometric mean peak anti-lipopolysaccharide responses in groups 1 to 4, respectively, were 99, 39, 278, and 233 for immunoglobulin (IgA) antibody-secreting cell counts; 401, 201, 533, and 284 for serum reciprocal IgG titers; and 25, 3, 489, and 1,092 for fecal IgA reciprocal titers. Postvaccination increases in gamma interferon production in response to Shigella antigens occurred in some volunteers. We conclude that WRSS1 vaccine is remarkably immunogenic in doses ranging from 10(3) to 10(6) CFU but elicits clinical reactions that must be assessed in further volunteer trials.

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References

Bernardini M, Mounier J, DHauteville H, Sansonetti P . Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin. Proc Natl Acad Sci U S A. 1989; 86(10):3867-71. PMC: 287242. DOI: 10.1073/pnas.86.10.3867. View

Black R, Levine M, Clements M, Losonsky G, Herrington D, Berman S . Prevention of shigellosis by a Salmonella typhi-Shigella sonnei bivalent vaccine. J Infect Dis. 1987; 155(6):1260-5. DOI: 10.1093/infdis/155.6.1260. View

Van de Verg L, Herrington D, Murphy J, Wasserman S, Formal S, Levine M . Specific immunoglobulin A-secreting cells in peripheral blood of humans following oral immunization with a bivalent Salmonella typhi-Shigella sonnei vaccine or infection by pathogenic S. sonnei. Infect Immun. 1990; 58(6):2002-4. PMC: 258758. DOI: 10.1128/iai.58.6.2002-2004.1990. View

Herrington D, Van de Verg L, Formal S, Hale T, Tall B, Cryz S . 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; 8(4):353-7. DOI: 10.1016/0264-410x(90)90094-3. View

Formal S, Oaks E, Olsen R, Snoy P, Cogan J . Effect of prior infection with virulent Shigella flexneri 2a on the resistance of monkeys to subsequent infection with Shigella sonnei. J Infect Dis. 1991; 164(3):533-7. DOI: 10.1093/infdis/164.3.533. View

Ferreccio C, Prado V, Ojeda A, Cayyazo M, Abrego P, Guers L . Epidemiologic patterns of acute diarrhea and endemic Shigella infections in children in a poor periurban setting in Santiago, Chile. Am J Epidemiol. 1991; 134(6):614-27. DOI: 10.1093/oxfordjournals.aje.a116134. View

Miller J, Barrett L, Kotloff K, Guerrant R . A rapid test for infectious and inflammatory enteritis. Arch Intern Med. 1994; 154(23):2660-4. DOI: 10.1001/archinte.1994.00420230043006. View

Kotloff K, Losonsky G, Nataro J, Wasserman S, Hale T, Taylor D . 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. DOI: 10.1016/0264-410x(94)00011-b. View

Reed G, Meade B, Steinhoff M . The reverse cumulative distribution plot: a graphic method for exploratory analysis of antibody data. Pediatrics. 1995; 96(3 Pt 2):600-3. View

10.

Marquart M, Picking W, Picking W . Structural analysis of invasion plasmid antigen D (IpaD) from Shigella flexneri. Biochem Biophys Res Commun. 1995; 214(3):963-70. DOI: 10.1006/bbrc.1995.2380. View

11.

Kotloff K, Nataro J, Losonsky G, Wasserman S, Hale T, Taylor D . A modified Shigella volunteer challenge model in which the inoculum is administered with bicarbonate buffer: clinical experience and implications for Shigella infectivity. Vaccine. 1995; 13(16):1488-94. DOI: 10.1016/0264-410x(95)00102-7. View

12.

Kotloff K, Noriega F, Losonsky G, Sztein M, Wasserman S, Nataro J . 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):4542-8. PMC: 174410. DOI: 10.1128/iai.64.11.4542-4548.1996. View

13.

Picking W, Mertz J, Marquart M, Picking W . Cloning, expression, and affinity purification of recombinant Shigella flexneri invasion plasmid antigens IpaB and IpaC. Protein Expr Purif. 1996; 8(4):401-8. DOI: 10.1006/prep.1996.0117. View

14.

Cohen D, Ashkenazi S, Green M, Gdalevich M, ROBIN G, Slepon R . Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults. Lancet. 1997; 349(9046):155-9. DOI: 10.1016/S0140-6736(96)06255-1. View

15.

Hartman A, Venkatesan M . Construction of a stable attenuated Shigella sonnei DeltavirG vaccine strain, WRSS1, and protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model. Infect Immun. 1998; 66(9):4572-6. PMC: 108562. DOI: 10.1128/IAI.66.9.4572-4576.1998. View

16.

Coster T, Hoge C, VanDeVerg L, Hartman A, Oaks E, Venkatesan M . Vaccination against shigellosis with attenuated Shigella flexneri 2a strain SC602. Infect Immun. 1999; 67(7):3437-43. PMC: 116529. DOI: 10.1128/IAI.67.7.3437-3443.1999. View

17.

Kotloff K, Winickoff J, Ivanoff B, Clemens J, Swerdlow D, Sansonetti P . Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ. 1999; 77(8):651-66. PMC: 2557719. View

18.

Samandari T, Kotloff K, Losonsky G, Picking W, Sansonetti P, Levine M . Production of IFN-gamma and IL-10 to Shigella invasins by mononuclear cells from volunteers orally inoculated with a Shiga toxin-deleted Shigella dysenteriae type 1 strain. J Immunol. 2000; 164(4):2221-32. DOI: 10.4049/jimmunol.164.4.2221. View

19.

Kotloff K, Noriega F, Samandari T, Sztein M, Losonsky G, Nataro J . 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):1034-9. PMC: 97245. DOI: 10.1128/IAI.68.3.1034-1039.2000. View

20.

Mel D, ARSIC B, Nikolic B, Radovanic M . Studies on vaccination against bacillary dysentery. 4. Oral immunization with live monotypic and combined vaccines. Bull World Health Organ. 1968; 39(3):375-80. PMC: 2554416. View