Study Evaluating Aerosol and Intradermal Administration of a Candidate Tuberculosis (TB) Vaccine, MVA85A, as a Way to Increase Immune Response and Avoid Anti-vector Immunity

A Phase I Trial Evaluating Mucosal Administration of a Candidate TB Vaccine, MVA85A, as a Way to Induce Potent Local Cellular Immune Responses and Avoid Anti-vector Immunity

Boost vaccinations sometimes have no effect because the body has got used to the vaccine and no longer reacts to it. We are therefore investigating whether vaccinating with aerosolised MVA85A (a candidate tuberculosis vaccine) followed by a boost MVA85A intradermal vaccination (or vice versa) avoids this and increases the immune response to vaccination.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: MVA85A

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to enter the trial:

• Healthy adult aged 18-55 years
• Resident in or near Oxford for the duration of the trial period
• No relevant findings in medical history or on physical examination
• Confirmation of prior vaccination with BCG not less than 6 months prior to projected trial vaccination date (by visible BCG scar on examination or written documentation)
• Allow the Investigators to discuss the individual's medical history with their GP
• Use effective contraception for the duration of the trial period (females only)
• Refrain from blood donation during the trial
• Give written informed consent
• Allow the Investigator to register subject details with a confidential database to prevent concurrent entry into clinical trials
• Able and willing (in the Investigator's opinion) to comply with all the trial requirements

Exclusion Criteria:

Subjects must meet none of the following criteria to enter the trial:

• Any respiratory disease, including asthma
• Current smoker
• Clinically significant abnormality on screening chest x-ray
• Clinically significant abnormality of pulmonary function tests
• Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
• Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs
• Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
• Clinical, radiological, or laboratory evidence of current active TB disease
• Previous vaccination with candidate vaccine MVA85A or candidate vaccine FP85A or any other recombinant MVA vaccine
• Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
• History of serious psychiatric condition
• Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
• History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccine, sedative drugs, or any local or general anaesthetic agents
• Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the subject in the trial
• Positive HBsAg, HCV or HIV antibodies
• Female currently lactating, confirmed pregnancy or intention to become pregnant during trial period
• Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the trial vaccine for 30 days prior to dosing with the trial vaccine, or planned use during the trial period
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
• Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the subject at risk or may influence the result of the trial or may affect the subject's ability to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Receive 5x10^7 MVA85A by aerosol at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.	Biological: MVA85A; Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.
Experimental: Group 2; Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost aerosol vaccination of 5x10^7 MVA85A at day 28.	Biological: MVA85A; Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.
Experimental: Group 3; Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.	Biological: MVA85A; Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of 5 x 10^7 pfu dose of MVA85A administered by aerosol and compared to the same dose administered intradermally	Actively and passively collected data on adverse events	24 weeks from enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of 5 x 10^7 pfu dose of MVA85A administered by aerosol followed by the same dose administered intradermally, compared to the same dose of MVA85A given intradermally and boosted by aerosol	Characterise mucosal and systemic immunogenicity of viral vector (MVA) and insert (Ag85A) by comprehensive characterisation of humoral and cellular immune responses; Evaluate functional relevance of anti-vector immunity induced by aerosol and systemic immunisation in MVA85A-prime followed by homologous MVA85A-boost administered 4 weeks later	24 weeks from enrolment

Collaborators and Investigators

• Sponsor: University of Oxford

Publications and helpful links

General Publications

• Manjaly Thomas ZR, Satti I, Marshall JL, Harris SA, Lopez Ramon R, Hamidi A, Minhinnick A, Riste M, Stockdale L, Lawrie AM, Vermaak S, Wilkie M, Bettinson H, McShane H. Alternate aerosol and systemic immunisation with a recombinant viral vector for tuberculosis, MVA85A: A phase I randomised controlled trial. PLoS Med. 2019 Apr 30;16(4):e1002790. doi: 10.1371/journal.pmed.1002790. eCollection 2019 Apr.

Helpful Links

• Jenner Institute Clinical Trials

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: September 26, 2013
• First Posted (Estimate): October 1, 2013

Study Record Updates

• Last Update Posted (Estimate): January 28, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Vaccine; Immunogenicity; Tuberculosis
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: TB035