Safety and immunogenicity of an oral, inactivated, whole-cell vaccine for Shigella sonnei: preclinical studies and a Phase I trial

McKenzie, Robin; Walker, Richard I.; Nabors, Gary S.; Verg, Lillian L. Van De; Carpenter, Colleen; Gomes, G. S.; Forbes, Emily K.; Tian, Jing; Yang, Huei-Hsiung; Pace, John; Jackson, W. James; Bourgeois, A. Louis

doi:10.1016/j.vaccine.2005.07.014

Cited by 61 publications

(45 citation statements)

References 28 publications

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“…Despite these modest immune responses, SC602 was protective in a challenge study in the United States. The immune response to LPS with Sf2aWC in our study was also comparable to the oral inactivated whole-cell vaccine for Shigella sonnei (SsWC), where four of seven vaccinees (57%) had IgG and IgA responses to LPS (30).…”

Section: Figsupporting

confidence: 66%

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Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects

Chakraborty

Harro

DeNearing

et al. 2016

Clin Vaccine Immunol

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Shigella causes high morbidity and mortality worldwide, but there is no licensed vaccine for shigellosis yet. We evaluated the safety and immunogenicity of a formalin-inactivated whole-cell Shigella flexneri 2a vaccine, Sf2aWC, given orally to adult volunteers. In a double-blind, placebo-controlled trial, 82 subjects were randomized to receive three doses of vaccine in dose escalation (2.6 ؎ 0.8 ؋ 10 8 , ؋ 10 9 , ؋ 10 10 , and ؋ 10 11 vaccine particles/ml). Vaccine safety was actively monitored, and antigen-specific systemic and mucosal immune responses were determined in serum, antibody in lymphocyte supernatant (ALS), and fecal samples. Cytokines were measured in the serum. Sf2aWC was well tolerated and generally safe at all four dose levels. The vaccine resulted in a dose-dependent immune response. At the highest dose, the vaccine induced robust responses to lipopolysaccharide (LPS) in both serum and ALS samples. The highest magnitude and frequency of responses occurred after the first dose in almost all samples but was delayed for IgG in serum. Fifty percent of the vaccinees had a >4-fold increase in anti-LPS fecal antibody titers. Responses to invasion plasmid antigens (Ipa) were low. The levels of interleukin-17 (IL-17), IL-2, gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), and IL-10 were increased, and IL-8 was decreased immediately after first dose, but these changes were very transient. This phase I trial demonstrated that the Sf2aWC vaccine, a relatively simple vaccine concept, was safe and immunogenic. The vaccine elicited immune responses which were comparable to those induced by a live, attenuated Shigella vaccine that was protective in prior human challenge studies. Shigella causes bacillary dysentery, a severe, intensely inflammatory gastrointestinal disease affecting the distal regions of the colon and the rectum. Shigellosis is a low-inoculum (10 to 100 organisms) infection that is readily transmitted by direct fecaloral contact. Most of the infections are associated with poor sanitation and contaminated water. Naturally acquired Shigella infection elicits antibody-mediated serotype-specific protective immunity (1, 2). According to the Global Enteric Multicenter Study (GEMS), Shigella was one of the most common pathogens responsible for the diarrheal disease burden and death in children ages 12 to 59 months in areas of Shigella endemicity (3, 4). Mortality from shigellosis has diminished significantly in the past 2 to 3 decades (5, 6), largely because of the virtual disappearance of the highly virulent Shiga toxin-producing Shigella dysenteriae 1 serotype worldwide. However, the pediatric morbidity due to other species of Shigella remains substantial (7,8). In the United States, 10,382 and 10,898 cumulative cases of shigellosis were reported in 2014 and 2015 (just through August of 2015), respectively (9). World Health Organization guidelines recommend antibiotic treatment for clinical dysentery (diarrhea with gross blood). However, Shigella frequently acquires resistance to antib...

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Section: Figsupporting

confidence: 66%

“…An inactivated WCV vaccine for S. sonnei formulated using a complicated fermentation process with 2.0 ϫ 10 10 vaccine particles (vp)/ml in a three-dose schedule was found to be effective in a phase I trial (30).…”

mentioning

confidence: 99%

Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects

Chakraborty

Harro

DeNearing

et al. 2016

Clin Vaccine Immunol

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“…and ETEC are also under development (Table 4; refs. [125][126][127][128][129][130][131][132][133][134][135][136][137]. Two approaches to develop vaccines to prevent infection with Shigella spp.…”

Section: Enteric Vaccinesmentioning

confidence: 99%

Enteric infections, diarrhea, and their impact on function and development

Petri¹,

Miller²,

Binder³

et al. 2008

J. Clin. Invest.

385

293

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Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.

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“…Heat-killed S. dysenteriae type 1 and S. flexneri induced IgG in serum and IgA in mucosa in guinea pigs, against the LPS of each microorganism, in addition to protection against homologous bacteria in a challenge study. 13 McKenzie et al 46 obtained a whole-cell vaccine by treatment of S. sonnei (grown in rich containing deoxycholate) with formalin, in order to boost the surface antigens. Two weeks after intranasal vaccination of the guinea pigs, using 2 £ 10 7 inactivated cells, the animals were challenged with pathogenic S. sonnei in a Sereny test.…”

Section: 45mentioning

confidence: 99%

“…A phase I trial of this vaccine candidate demonstrated that it is well tolerated by human volunteers, inducing an immunogenic response, as all individuals had immunoglobulins reacting to at least 1 of the antigens studied. 46 Moreover, a recent study adjusted the formalin concentrations and incubation temperatures to obtain a trivalent inactivated Shigella whole-cell vaccine, which includes S. flexneri 2a, 3a and S. sonnei. Intranasal immunization of guinea pigs protected against the corresponding pathogenic bacterium in a Sereny test.…”

Section: 45mentioning

confidence: 99%

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

O’Ryan

Vidal

Canto

et al. 2015

Human Vaccines & Immunotherapeutics

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Safety and immunogenicity of an oral, inactivated, whole-cell vaccine for Shigella sonnei: preclinical studies and a Phase I trial

Cited by 61 publications

References 28 publications

Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects

Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects

Enteric infections, diarrhea, and their impact on function and development

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

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