safety and tolerability of a bioconjugate vaccine against shigella flexneri 2a

Conditions: Shigellosis

Summary: this is a phase i, single-blind, randomized, placebo-controlled, single-center study in healthy subjects using a staggered approach to dosing. 30 subjects will be randomized to receive 10 μg flexyn2a candidate vaccine with or without adjuvant or placebo.

a total of 30 subjects will be randomly assigned to one of 3 different arms in order to evaluate the safety, tolerability and immunogenicity of a candidate vaccine, formulated with or without adjuvant, and the outcome compared to a placebo control group. for each active treatment group, 12 subjects will be injected twice with 10 μg flexyn2a candidate vaccine 4 weeks apart. a control group with 6 subjects will be injected following the same schedule with a placebo solution.

Eligibility criteria:
inclusion criteria: 1. healthy male or female volunteers, age of 18 to 50 years (inclusive) at the time of enrollment. 2. signed informed consent form. 3. completion and review of comprehension test (achieved \>70% accuracy) 4. available for the required follow-up period and scheduled clinic visits. 5. women: negative pregnancy test with understanding (through informed consent process) to not become pregnant or or breastfeed during the study or within twelve (12) weeks after the last vaccine dose. exclusion criteria: 1. health condition that, in the opinion of the investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of adverse events (aes). study clinicians, in consultation with the pi, will use clinical judgment on a case by-case basis to assess safety risks under this criterion. the pi will consult with the research monitor as appropriate. 2. clinically significant abnormalities on physical examination. 3. clinically significant abnormalities on basic laboratory screening. 4. presence of significant unexplained laboratory abnormalities that, in the opinion of the pi, may potentially confound the analysis of the study results 5. regular use of constipation, antacid or anti-diarrheal medications or treatments. 6. abnormal stool pattern (fewer than 3 stools per week or more than 3 per day) or loose/liquid stools more than occasionally. 7. use of immunosuppressive drugs such as corticosteroids or chemotherapeutics that may influence antibody development. 8. women currently nursing. 9. participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) within 30 days of planned date of first vaccination or anytime throughout the duration of the study. 10. positive blood test for hbsag, hepatitis c virus (hcv), hiv-1. 11. positive blood test for hla-b27. 12. immunosuppressive illness or immunoglobulin deficiency (serum immunoglobulin a level \< 7 mg/dl or limit of detection of assay). 13. family history of congenital or hereditary immunodeficiency. 14. treatment with immunoglobulins or blood products within 3 months from first candidate vaccine injection. 15. history of microbiologically confirmed shigella infection. 16. personal or family history of inflammatory arthritis. 17. personal or family history of irritable bowel syndrome. 18. received previous experimental shigella vaccine or live shigella challenge. 19. have had diarrhea while traveling outside the united states or lived for 2 or more months during the past 3 years in a country with potentially higher shigella infection rates, including africa, south america, central america, and asia (except japan). 20. occupation involving handling of shigella bacteria currently, or in the past 3 years. 21. history of allergy to any vaccine. 22. history of allergy to aluminum hydroxide. 23. serum immunoglobulin g endpoint titer ≥ 2500 to shigella lipopolysaccharide.

Keywords: bioconjugate vaccine safety immunogenicity shigellosis