Malaria Candidate Vaccines FP9 Circumsporozoite (CS) and MVA CS in Adult Gambian Men
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Animal and human studies have shown that the prime-boost immunization strategy using malaria
      antigens expressed in plasmid or viral vectors induces strong cellular immune responses. An
      immunization regimen with the malaria vaccines DNA ME-TRAP followed by MVA ME-TRAP induced
      strong T cell responses in adults in the United Kingdom (UK) and in the Gambia but did not
      provide significant clinical protection against infection. The investigators assessed two new
      vaccines which utilize a similar immunization strategy but a different malaria antigen, a
      circumsporozoite (CS) protein. The entire CS protein was expressed either in a modified
      vaccinia virus Ankara (MVA) CS, or an attenuated fowlpox virus strain (FP9) CS.
    

Detailed description: 
      Objectives:

      The primary aim was the assessment of safety and reactogenicity of these vaccines in Gambian
      adults. The secondary aim was the assessment of immunogenicity and comparison with UK adults
      given the same vaccines.

      Study Area:

      The study was conducted in the town of Farafenni, about 200km east of the capital city,
      Banjul. In this area, malaria is highly seasonal with an entomological inoculation rate
      between 10-50 bites per year. This study was carried out from January to June, when the
      incidence of malaria is low.

      Study Population:

      The study involved 32 healthy Gambian adults aged 18-45 years. Volunteers were subjected to a
      thorough physical and medical examination. Exclusion criteria included a low PCV (< 30%);
      raised plasma creatinine or ALT levels; and HIV positivity, as determined by ELISA assays.

      Study Procedure:

      After prior consultations with community leaders, public meetings were held to inform the
      community of the planned study. Volunteers aged 18-45 years were then invited to take part in
      the study after written informed consent was obtained in the presence of the principal
      investigator. Prior to the start of the screening exercise, the investigators checked the age
      and identity of each volunteer and conducted pre-HIV test counselling. Screening involved a
      thorough physical examination, blood sampling for haematological (full blood count, packed
      cell volume [PCV]), renal (plasma creatinine) and hepatic (alanine aminotransferase) tests
      and HIV 1 and 2 testing by ELISA. All eligible volunteers were issued unique study numbers
      and photo identification cards.

      The initial part of the study was designed to determine the dose and safety of the individual
      vaccines using an open-label dose escalation method. Study volunteers were randomly allocated
      to two groups of four that received 5 x 10^7 pfu id of either FP9 CS or MVA CS. When a good
      safety profile was evident one week after this dose, another set of four volunteers per group
      received a higher dose (1 x 10^8 pfu id) of FP9 CS or MVA CS. After the investigators had
      achieved a satisfactory safety profile with a higher dose of both vaccines given alone, they
      proceeded to administer the vaccines in combination using the heterologous prime-boost
      regime. The vaccines were administered at 4-week intervals. Eight volunteers received FP9 CS
      at week 0 followed by MVA CS at week 4 (FM group). Another set of 8 volunteers received FP9
      CS at weeks 0 and 4, followed by MVA CS at week 8 (FFM). Following vaccination, volunteers
      were observed for 1 hour and given a course of antipyretic (paracetamol) to take if required.
      A physician and a study nurse could be contacted by the volunteers at anytime during the
      course of the study. In addition, home visits were made by field workers on days 1, 2, 7 and
      28, after each vaccination, to record adverse events using a standard questionnaire.

      Sample Size:

      Sample size was determined by the requirement to make a preliminary evaluation of inter-group
      and inter-individual variability, to avoid excessive risk and to allow for a realistic
      workload. Statistical significance may not be reached in this study with low power, but a
      non-significant finding would provide justification for the need for a study with greater
      power.

      Data Safety Monitoring Board (DSMB):

      An international DSMB was established to monitor the conduct of the trial and to approve the
      analytical plan. The trial was conducted in line with the ICH Good Clinical Practices
      guidelines and with the Medical Research Council (MRC) rules and regulations for the conduct
      of clinical trials.
    

Intervention name(s): FP9 CS; MVA CS
Intervention type(s): Biological; Biological
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria; Vaccines; Safety; Immunogenicity