SEmalvac

Serine repeat antigen-5 malaria vaccine

Watch these interesting videos and learn more about Japanese - Global Health Innovative Technology Fund (GHIT) - efforts to combat malaria in Burkina Faso:

GHIT annual partners meeting

session 1 "innovation and impact"

GHIT on the ground

https://youtu.be/Nq6u_cCzn4k
https://youtu.be/dtZPEBG9ljM

https://youtu.be/VLKCzTJ_U0Q
https://youtu.be/n0ZwRsOzlgU

 

Background

The Plasmodium falciparum serine repeat antigen-5 (SERA5) is an abundant blood stage antigen produced and secreted in large amounts in the parasitophorous vacuole at late trophozoite and late schizont stages1.  It plays an essential role in the parasite life cycle and was among the first physiological substrate identified for a serine protease implicated for parasite egress2.  A recombinant form of SERA5 N-terminal domain (SE36) was selected for clinical development on the basis of the following: (i) epidemiological studies showing high antibody titres that inversely correlate with malaria symptoms and severe disease; (ii) in vitro studies demonstrating induction of antibodies that are inhibitors of parasite growth, exert antibody-dependent complement-mediated lysis of schizonts, or antibody-dependent monocyte-mediated parasite growth inhibition; and (iii) animal studies demonstrating protection against P. falciparum challenge in non-human primates. 

SE36 was prepared under current Good Manufacturing Practice (cGMP) constraints and formulated with aluminium hydroxide gel to yield BK-SE36.  The safety and immunogenicity of BK-SE36 was demonstrated in a phase Ia clinical trial in malaria naive Japanese adults3, and in a phase Ib trial conducted in healthy subjects aged 6–32 years from a malaria endemic area in Northern Uganda4.

Objectives

The main objective of the SEmalvac project funded by the Global Health Innovation Technology (GHIT) Fund is to assess the safety and immunogenicity of the recombinant Escherichia coli BK-SE36 malaria vaccine candidate in healthy malaria exposed African children aged 1-5 years living in Burkina Faso.  The phase Ib trial will (i) test the vaccine candidate in a younger age group (1-5 years), (ii) generate additional information/data on safety, immunogenicity and possible efficacy, and (iii) allow comparison of clinical trial results from two African countries with different malaria endemicity - Uganda (from the previous clinical trial) and Burkina Faso.  .

A second objective of the SEmalvac project is to conduct a one-year follow-up study of Japanese naive healthy volunteers from a previous phase Ia trial in which safety and immunogenicity of the BK-SE36 vaccine candidate in combination with the K3 CpG adjuvant were evaluated.  The follow-up will enable long-term data on the safety and the durability of the antibody response to be obtained.

Milestones

Phase Ib in Burkina Faso:

  • Submission of the Investigational Medicinal Product Dossier and final clinical protocol to the Independent Ethics Committees (IECs) and Regulatory Authorities in Burkina Faso - Q1 2015
  • Approval of the IECs and Regulatory Authorities - Q2 2015
  • Last visit last subject - Q3 2016
  • Safety report - Q4 2016

Follow-up BK-SE36/CpG study:

  • Subject agreement to participate in the follow-up study - Q3 2014
  • Completion of one-year follow-up - Q4 2016

Major Achievements

  • Registration of the BK-SE36 clinical trial at the Pan Africa Clinical Trial Registry (PACTR): N° PACTR2014110009341208
  • In Q2 2015 the SEmalvac clinical trial application received ethical clearance and approval from the regulatory authorities in Burkina Faso to commence the phase Ib clinical trial. 

References

  1. Fox BA, Bzik DJ (1994). Analysis of stage-specific transcripts of the Plasmodium falciparum serine repeat antigen (SERA) gene and transcription from the SERA locus. Mol Biochem Parasitol; 68(1):133-44.
  2. Yeoh S, O’Donnell RA et al. (2007). Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131:1072-1083
  3. Horii T, Shirai H et al. (2010). Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36. Parasitol Int 59: 380-386
  4. Palacpac NMQ, Ntege E et al. (2013). Phase Ib randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36. Plos One 8(5): e64073. doi: 0.1371/journal.pone.0064073

Participants at the SEmalvac annual meeting 2015, Burkina Faso, 04-07 May 2015
Participants at the SEmalvac annual meeting 2015, Burkina Faso, 04-07 May 2015