NCT00866476

Safety and Efficacy Study of CVD 1208S, a Live, Attenuated Oral Vaccine to Prevent Shigella Infection: Phase IIa

Safety, Immunogenicity, and Efficacy Following Experimental Challenge of CVD 1208S, a Delta guaBA, Delta Sen, Delta Set Shigella Flexneri 2a Live, Oral Vaccine: Phase IIa Vaccination Study

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of Maryland, Baltimore · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to determine whether CVD 1208S (a live, attenuated, oral vaccine) is safe and effective in the prevention of Shigella infection.

Detailed description

The study comprises a Phase 2 vaccination study and a Phase 2b challenge study. The primary objectives of the Phase 2 vaccination study are: 1. To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of an investigational, live, oral, attenuated vaccine called CVD 1208S, with particular attention to the occurence of diarrhea, dysentery, and fever, and 2. To characterize immune responses following ingestion of this vaccine. The primary objective of the Phase 2b challenge study is to measure the protective efficacy of 3 spaced doses of vaccine after ingestion of an oral challenge strain called Shigella flexneri 2a strain 2457T. Shigella is a leading cause of disease and death among children younger than 5 years living in developing countries. The difficulty controlling this infection has led experts to believe that prevention with the use of a vaccine is a promising strategy. At the CVD, we have pursued an approach of developing an oral, attenuated Shigella vaccine that prevents infection with the Shigella types of greatest clinical and epidemiologic importance. One of the strains to be included in the vaccine is called Shigella flexneri 2a. Investigators at the CVD have created a vaccine from Shigella flexneri 2a, designated CVD 1208S, using molecular biology techniques. To date, nearly 40 subjects have received varying doses of this vaccine with good clinical tolerance and modest immunogenicity. Previously a single dose of vaccine was used. In the current study, we will administer doses of vaccine on days 0, 28, and 56 to attempt to maximize immunogenicity. Approximately one month after the 3rd dose, a group of \~15-20 vaccinated volunteers along with a similar number of unvaccinated control subjects will be admitted to the CVD Research Isolation Ward at SNBL and challenged with wild type Shigella flexneri 2a. By comparing the attack rate of illness in vaccinated vs. unvaccinated subjects, we will determine the vaccine's ability to confer protective immunity.

Conditions

• Shigella

Interventions

Type	Name	Description
BIOLOGICAL	CVD 1208S, a Shigella flexneri 2a live, oral vaccine	CVD 1208S consists of freshly harvested ∆guaBA, ∆sen, ∆set S. flexneri 2a strain 2457T suspended in phosphate buffered saline to reach the desired inoculum Form: liquid Dose: 10 to the 9th power CFU in 1.0 ml Route: oral.
OTHER	Placebo	30 ml of buffer solution (2.0 grams of NaHCO3 dissolved in 150 ml of sterile water) without bacteria, to which food grade corn starch, USP is added, as necessary, to match the turbidity of the vaccine inoculum

Timeline

• Start date: 2010-01-01
• Primary completion: 2010-02-01
• Completion: 2010-02-01
• First posted: 2009-03-20
• Last updated: 2021-04-29

Locations

1 site across 1 country: United States