Persistence of the Immune Response After Immunisation With Ebola Virus Vaccines
Condition: Ebola Virus Disease
MeSH terms: Virus Diseases; Hemorrhagic Fever, Ebola
Study type: Observational

Summary: 
      The aim of this study is to investigate the persistence of the vaccine induced immune
      response between 24 - 60 months following primary vaccination.

      The study consists of three cohorts:

      Cohort 1: volunteers from the Phase 1 study of the various prime/boost regimes with two viral
      vectored Ebola vaccines: Ad26-ZEBOV and MVA-BN-Filo vaccines

      Cohort 2: volunteers who have been vaccinated previously with Ebola vaccine r-VSV-ZEBOV

      Cohort 3: volunteers from the Phase 2 study of 3 prime/boost regimes with Ad26.ZEBOV and
      MVA-BN-Filo vaccines (VAC52150EBL2001: EVOLVE).
    

Detailed description: 
      The Ebola Virus Disease (EVD), is caused by the viruses belonging to the genus Ebola virus.
      The disease occurs in sporadic outbreaks in the endemic zones of Africa and results in high
      mortality. During an outbreak, human to human to transmission occurs by contact with the body
      fluids of an infected individual. In the inter-endemic period the disease is zoonotically
      sustained in the environment. Prevention or control of future endemic outbreaks in the high
      risk areas of Africa will require effective preventative strategies including immunisation.

      Cohort 1:

      The Phase 1 study with the multiple heterologous prime boost regimes of the Ad26-ZEBOV and
      the MVA-BN-Filo vaccines demonstrated a substantive immunogenicity and safety of the
      vaccines. A combined immune response of humoral and cellular immunity was observed in the
      study participants. Furthermore, persistence of the immune response was evident at one year
      following the primary vaccination. It is not known whether the immune response persists
      beyond this time point. The duration of the immunological response is important as it will
      inform the clinical utility of the vaccines and whether or not additional booster dosage will
      be required and if so, at what interval.

      In this study we will invite the 56 participants from the Phase 1 study at two time points:
      24 - 30 months and 36 - 48 months after receiving the primary vaccination. Following
      consenting and enrolment into the study, the participants will undergo a blood test. We will
      assess the humoral immunity by estimating the level of binding antibody to the Ebola virus
      envelope glycoprotein. Cellular immunity will be assessed by estimating the functional CD4+
      and the CD8+ T cells secreting the pro-inflammatory cytokines. We will undertake this
      assessment by intracellular staining of the peripheral blood mononuclear cells (PBMC) and
      using flowcytometry technique to identify the positively stained cells. A second assessment
      of the cellular immunity will be carried out by an in-house ELISpot technique subject to
      availability of additional funding.

      Cohort 2:

      In October 2015, contacts of a laboratory-confirmed case of Ebola virus diseases (EVD) in the
      U.K. were given the rVSV-EBOV vaccine as a part of clinical preventative care. Subsequently,
      these recipients of the rVSV-EBOV vaccine were enrolled and followed up for safety and immune
      response until one year post vaccination in the Glasgow Ebola Vaccine Follow-up Study (REC
      reference 15/WS/0251). The duration of persistence of the immune response to rVSV-EBOV beyond
      360 days is unknown and may impact on the use of the vaccine in any future Ebola outbreaks.
      This study provides an opportunity to study the immune response beyond 1 year from the prime
      vaccination and to compare those results with the response to MVA-BN-Filo and Ad26-ZEBOV
      vaccines. This study will also allow for a further period of safety follow-up for this
      cohort.

      Twenty-six individuals were vaccinated with the r-VSV-EBOV Ebola vaccine in Glasgow following
      possible exposure to a patient with confirmed Ebola virus disease as a part of preventative
      clinical care. All 26 individuals will be invited to take part in this study.

      Cohort 3:

      This cohort consists of participants from the Phase 2 study of 3 prime/boost regimes with
      Ad26.ZEBOV and MVA-BN-Filo vaccines (VAC52150EBL2001: EVOLVE). This was a randomized,
      observer-blind, placebo-controlled, parallel-group, multicentre, Phase 2 study to evaluate
      the safety, tolerability and immunogenicity of 3 heterologous prime-boost regimens which
      differed in the timing of the boost vaccination. The dose of each study vaccine (Ad26.ZEBOV,
      MVA-BN-Filo or placebo) and the sequence of vaccination were identical in each group. The
      prime/boost regimens were commenced in July 2015 and completed in February 2016.

      Recruitment of participants in Group 1 (unblinded) of EVOLVE into the PRISM study can
      commence once all approvals are in place. However, for participants in Group 2 (blinded) of
      the EVOLVE study, recruitment and enrolment will not commence until after EVOLVE has been
      unblinded (anticipated to occur in Q4 2018 - Q1 2019).
    

Intervention name(s): Previously exposed to Ebola vaccine
Intervention type(s): Biological
Intervention description(s): Exposure of interest: participants must have had one or more previous Ebola vaccines, Ad26.ZEBOV , MVA-BN-Filo or r-VSV-ZEBOV to enter the study.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Cohort 1: 56 Phase 1 study participants who have received both Ad26-ZEBOV and the
        MVA-BN-Filo vaccines and who meet the inclusion and exclusion criteria as listed above .

        Cohort 2: 26 participants who received r-VSV-ZEBOV vaccine as a part of clinical
        preventative care.

        Cohort 3: 148 Phase 2 study participants who have received both Ad26-ZEBOV and the
        MVA-BN-Filo vaccines and who meet the inclusion and exclusion criteria as listed above
      
Biospecimen description: 
      We will seek consent for storage of excess blood samples in the Biobank. Participants will be
      separately consented for this.
    
Keywords: Ebola vaccine; immunogenicity; persistence