Delving into the Latest Updates on Live attenuated Shigella sonnei vaccine Wrss2 (National Institute of Allergy & Infectious Diseases) with Synapse

Overview

Basic Info

Drug Type

Live attenuated vaccine, Prophylactic vaccine

Synonyms

Live Attenuated Shigella Sonnei Vaccine(National Institute of Allergy & Infectious Diseases), 志贺菌减毒活疫苗(National Institute of Allergy & Infectious Diseases)

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases

Active Indication

Dysentery, Bacillary

Inactive Indication-

Originator Organization

National Institute of Allergy & Infectious Diseases

Active Organization

National Institute of Allergy & Infectious Diseases

Inactive Organization

Walter Reed Army Institute of Research

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10^6 cfu or 5X10^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G.

Start Date12 Oct 2022

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT01336699 / CompletedPhase 1IIT

Safety and Immunogenicity of Two Live, Attenuated Oral Shigella Sonnei Vaccines: WRSs2 and WRSs3

Phase 1, randomized, double-blind, placebo controlled, dose-escalation, inpatient study of single doses of S. sonnei. Health adult subjects, ranging in age from 18 to 45 years of age (inclusive) will be screened. Enroll serial groups up to 90 subjects. The primary objective is to evaluate safety and tolerance of WRSs2 by monitoring presence, frequency and severity of clinical signs and symptoms. A secondary objective is to evaluate the immune response in blood and stool following ingestion of WRSs2 and WRSs3.

Start Date07 Jan 2013

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with Live attenuated Shigella sonnei vaccine Wrss2 (National Institute of Allergy & Infectious Diseases)

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100 Translational Medicine associated with Live attenuated Shigella sonnei vaccine Wrss2 (National Institute of Allergy & Infectious Diseases)

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100 Patents (Medical) associated with Live attenuated Shigella sonnei vaccine Wrss2 (National Institute of Allergy & Infectious Diseases)

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Literatures (Medical) associated with Live attenuated Shigella sonnei vaccine Wrss2 (National Institute of Allergy & Infectious Diseases)

01 Aug 2018·VaccineQ3 · MEDICINE

A Phase I trial to evaluate the safety and immunogenicity of WRSs2 and WRSs3; two live oral candidate vaccines against Shigella sonnei

Q3 · MEDICINE

Article

Author: Alexander, William ; Barnoy, Shoshana ; Suvarnapunya, Akamol E ; Kaminski, Robert W ; Baqar, Shahida ; McNeal, Monica ; Frenck, Robert W ; Baughman, Holly ; Dickey, Michelle ; Hoeper, Amy ; El-Khorazaty, Jill ; Venkatesan, Malabi M

Effective vaccines are needed to combat diarrheal diseases due to Shigella. Two live oral S. sonnei vaccine candidates, WRSs2 and WRSs3, attenuated principally by the lack of spreading ability, as well as the loss of enterotoxin and acyl transferase genes, were tested for safety and immunogenicity. Healthy adults 18-45 years of age, assigned to 5 cohorts of 18 subjects each (WRSs2 (n = 8), WRSs3 (n = 8) or placebo (n = 2)) were housed in an inpatient facility and administered a single oral dose of study agent 5 min after ingestion of oral bicarbonate. Ascending dosages of vaccine (from 10³ CFU to 10⁷ CFU) were evaluated. On day 8, treatment with ciprofloxacin (500 mg BID for 3 days) was initiated and subjects were discharged home 2 days after completing antibiotics. Subjects returned for outpatient visits on day 14, 28 and 56 post-vaccination for monitoring and collection of stool and blood samples. Both WRSs2 and WRSs3 were generally well tolerated and safe over the entire dose range. Among the 80 vaccinees, 11 subjects developed diarrhea, 8 of which were mild and did not affect daily activities. At the 10⁷ CFU dose, moderate diarrhea occurred in one WRSs2 subject while at the same dose of WRSs3, 2 subjects had moderate or severe diarrhea. Vaccinees mounted dose-dependent mucosal and systemic immune responses that appeared to correlate with fecal shedding. S. sonnei vaccine candidates WRSs2 and WRSs3 are safe and immunogenic over a wide dose range. Future steps will be to select the most promising candidate and move to human challenge models for efficacy of the vaccine.

01 Aug 2011·VaccineQ3 · MEDICINE

Shigella sonnei vaccine candidates WRSs2 and WRSs3 are as immunogenic as WRSS1, a clinically tested vaccine candidate, in a primate model of infection

Q3 · MEDICINE

Article

Author: T.L. Hale ; T. Collins ; R.W. Kaminski ; R.T. Ranallo ; K. Nemelka ; S. Baqar ; S. Barnoy ; M.M. Venkatesan

Shigella causes diarrhea and dysentery through contaminated food and water. Shigella sonnei live vaccine candidates WRSs2 and WRSs3 are attenuated principally by the loss of VirG(IcsA) that prevents bacterial spread within the colonic epithelium. In this respect they are similar to the clinically tested vaccine candidate WRSS1. However, WRSs2 and WRSs3 are further attenuated by loss of senA, senB and WRSs3 also lacks msbB2. As previously shown in cell culture assays and in small animal models, these additional gene deletions reduced the levels of enterotoxicity and endotoxicity of WRSs2 and WRSs3, potentially making them safer than WRSS1. However the behavior of these second-generation VirG(IcsA)-based vaccine candidates in eliciting an immune response in a gastrointestinal model of infection has not been evaluated. In this study, WRSs2 and WRSs3 were nasogastrically administered to rhesus monkeys that were evaluated for colonization, as well as for systemic and mucosal immune responses. Both vaccine candidates were safe in rhesus monkeys and behaved comparably to WRSS1 in bacterial excretion rates that demonstrated robust intestinal colonization. Furthermore, humoral and mucosal immune responses elicited against bacterial antigens appeared similar in all categories across all three strains indicating that the additional gene deletions did not compromise the immunogenicity of these vaccine candidates. Based on data from previous clinical trials with WRSS1, it is likely that, WRSs2 and WRSs3 will not only be safer in human volunteers but will generate comparable levels of systemic and mucosal immune responses that were achieved with WRSS1.

01 Jul 2011·Gut MicrobesQ2 · MEDICINE

Further characterization ofShigella sonneilive vaccine candidates WRSs2 and WRSs3-plasmid composition, invasion assays and Sereny reactions

Q2 · MEDICINE

Article

Author: Suvarnapunya, Akamol E ; Venkatesan, Malabi M ; Fonseka, Suramya ; Ranallo, Ryan T ; Lee, James E ; Boren, Tara ; Bedford, Lisa ; Barnoy, Shoshana

Shigella sonnei live vaccine candidates WRSs2 and WRSs3 are principally attenuated by the loss of the virG(icsA) gene that prevents bacterial spread. In addition both strains lack enterotoxin SenA and a paralog SenB. WRSs3 also has a deletion in the gene encoding MsbB2. Both of these vaccine candidates are expected to be improved safer versions of WRSS1 that only lacked the virG(icsA) gene and was reactogenic in volunteer trials. During the construction of WRSs2 and WRSs3, segments of the virulence plasmid spanning two FRT sites were found to be inverted in orientation. These inversions have been analysed to show that the overall composition of the plasmid is unaltered. Furthermore, characterization of WRSs2 and WRSs3 in a cell culture and in an animal model have conclusively demonstrated that the segment inversions per se do not adversely affect the behavior of these vaccine candidates and pose no increased safety risk for human evaluation.

100 Deals associated with Live attenuated Shigella sonnei vaccine Wrss2 (National Institute of Allergy & Infectious Diseases)

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