Vaccination designed to prevent infection with Shigella bacterial species (Shigella flexneri 2a, 3a, 6 and S. sonnei) and risk of shigellosis, sepsis and death. Infections and Infestations
Conditions
Interventions
The study will recruit healthy adults aged 18 to 55 years old who will first have a screening visit to confirm suitability for the trial. On enrolment, participants will be enrolled into 1 of 2 group
Sponsors
LimmaTech Biologics AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give informed consent for participation in the trial. 2. Male or Female, aged 18-55 years inclusive at time of vaccination. 3. In good health as determined by medical history, physical examination and clinical judgment of the study team. 4. Female participants of childbearing potential must be willing to ensure that they use highly effective contraception during the trial 5. In the Investigator’s opinion, is able and willing to comply with all trial requirements. 6. Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of diaries 7. Willing to provide their national insurance number or passport number to be registered on The Over-Volunteering Prevention System (TOPS). 8. Agree to allow study staff to access the participant's NHS health records, vaccination records and medical history as required for study purposes and to allow his or her GP (and/or Consultant if appropriate), to be notified of participation in the study. 9. Agree to refrain from donating blood for the duration of the study.
Exclusion criteria
Exclusion criteria: 1. History of significant organ/system disease that could interfere with the trial conduct or completion in the clinical judgement of the investigators. This includes any history of significant disease in the following: 1.1. Cardiovascular disease including congenital heart disease, previous myocardial infarction, valvular heart disease (or history of rheumatic fever), previous bacterial endocarditis, history of cardiac surgery (including pacemaker insertion), personal or family history of cardiomyopathy or sudden adult death 1.2. Respiratory disease such as uncontrolled asthma and chronic obstructive pulmonary disease 1.3. Endocrine disorders such as diabetes mellitus and Addison’s disease 1.4. Renal or bladder disease 1.5. Biliary tract disease 1.6. Gastro-intestinal disease such as inflammatory bowel disease, abdominal surgery within the last two years, coeliac disease and liver disease (including hepatitis B or C infection) 1.7. Neurological disease such as seizures and myasthenia gravis 1.8. Haematological disease including coagulation problems 1.9. Metabolic disease such as glucose-6-phosphate dehydrogenase deficiency 1.10. Psychiatric illness requiring hospitalisation 1.11. Depression, anxiety or other psychiatric illness whose severity is deemed clinically significant by the study investigators 1.12. Known or suspected drug and/or alcohol misuse (alcohol misuse defined as an intake exceeding 42 units per week) 1.13. Non-benign cancer, except squamous cell or basal cell carcinoma of the skin and cervical carcinoma in situ 2. Have any known or suspected impairment or alteration of immune function, resulting from, for example: 2.1. Congenital or acquired immunodeficiency (including IgA deficiency) 2.2. Human Immunodeficiency Virus infection or symptoms/signs suggestive of an HIV-associated condition 2.3. Autoimmune disease 2.4. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid therapy (including for more than 7 days consecutively within the previous 3 months). 3. Study significant abnormalities on screening investigations, that are either unlikely to resolve or do not resolve on repeat testing (at the discretion of an Investigator) within the recruitment timeline of the study 4. Have participated in previous Shigella species vaccination study 5. Receipt of a live or live attenuated vaccine within 4 weeks prior to vaccination or inactivated vaccine within 7 days prior to vaccination, or receipt of any vaccine other than the study vaccine within 4 weeks after any study vaccination. 6. Any history of allergy or anaphylaxis to a previous vaccine or vaccine component 7. Receipt of immunoglobulin or any blood product transfusion within 3 months of study start 8. Participation in another research study involving an investigational product or that which may compromise the integrity of the study (e.g. significant volumes of blood already taken in previous study) in the past 12 weeks, or are planning to do so within the trial period 9. Planned donation of blood/blood products outside of the study and during the trial period. 10. Inability, in the opinion of the Investigator, to comply with all study requirements including likelihood of successful venepuncture during the trial 11. Female participants who are pregnant, breastfeeding/lactating or planning pregnancy during the course of the study 12. Weight less than 50kg or a BMI < 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Assess the safety, tolerability and reactogenicity of the Shigella4V candidate vaccine: 1.1. The recording and assessment of local and systemic adverse events following administration of the vaccine. 1.2. Any other medically attended Adverse Event , Serious Adverse Event or Suspected Unexpected Serious Adverse Reaction starting from date of vaccination (D0) and for the following one hundred and sixty eight days (D168) 2.Assess immunogenicity of two different bioconjugate doses and establish an International Standard for anti-Shigella serum (human): Level of serum IgG against the 4 Shigella vaccine-serotypes will be tested by ELISA or similar assays, pre and post vaccination, in the two arms. International serum standard will be generated using ELISA methods on 400ml of blood per participant. The standard will be assigned a value for anti-S. flexneri 2a, anti-S. flexneri 3a, anti-S. flexneri 6 and anti-S. sonnei based on reactivity to the relevant LPS O-antigens in immunoassays. Values for IgG and IgA will be assigned to the International Standard | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory immunology to look at the level of serum IgG against the 4 Shigella vaccine-serotypes at additional timepoints following vaccination and the changing features of the participant immune response including innate, antibody and cell-mediated responses from vaccination to 6-months post-vaccination. Adaptive, innate, humoral, cell-mediated and mucosal responses to vaccination at baseline and post-vaccination time points, D0, D7, D28 and D168 using immunological laboratory assays | — |
Countries
England, United Kingdom
Contacts
Public ContactDenis Murphy
Outcome results
None listed