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Horii Lab／Endowed Chair  Department of Malaria Vaccine Development

Malaria is widespread in tropical and subtropical regions, and millions of people, particularly in Africa, remain at risk of disease and death despite substantial progress in malaria control. No effective malaria vaccine has been developed or licensed. Our laboratory is undertaking basic research and conducting clinical trials on our own candidate vaccine antigen gene.

Malaria vaccine targeting SERA

 The treatment of malaria patients is completely dependent on the efficacy of anti-malaria drugs, however, drug-resistant 
parasites are emerging. Although a malaria vaccine is the ideal weapon against this pathogen, vaccine development is hampered by genetic polymorphisms in candidate antigen genes. 
We have been focusing on the SERA5 molecule of P. falciparum and developing malaria vaccine NPC-SE36 by utilizing a recombinant SE36 protein. Epidemiological studies in malaria hyper-endemic areas showed that children with antibodies against SE36 experienced few or no symptomatic/clinical malaria, albeit such children are a minority. 
It was surprising that Ugandan adults that suffered umerous malaria infections did not respond to vaccination with NPC-SE36. By contrast, malaria-naive Japanese adults produced high levels of antibodies. Moreover, in young Ugandan children that experienced few malaria episode, we observed good antibody response. We obtained 72 % protective efficacy 1 year post-2nd-vaccination in a follow-up study of 6-20 years old in the phase lb trial. We have conducted Phase lb clinical trial of NPC-SE36 in Burkina Faso in west Africa in 2015-2017. Vaccine was well tolerated, and it was found that the immune response in 1 year infants group was much higher than children 2-5 years old. We have also completed Phase lb clinical trial (adult to 1 year baby) of NPC-SE36 with CpG adjuvant that stimulates innate immunity resulting in a significant immune response without safety concern. Phase II clinical trial is under planning.

Molecular strategy for malaria parasite survival and a function of SE36 protein

The malaria parasite develops highly sophisticated strategies to evade the human immune system. One of the most difficult phenomena encountered by those developing vaccines is genetic polymorphism of vaccine candidate genes; that is, field-isolated parasites harbor different sequences from the vaccine candidate genes. Fortunately, SE36 is highly homologous among malaria parasites worldwide. Recently we have shown that SE36 protein tightly binds to host vitronectin as cytoadherence molecule on the surface of parasite cell, merozoite, and vitronectin further binds to over 30 different host proteins for molecular camouflage from host immune system. Presentation of SE36/vitronectin complex to host immune system by repeated infections may cause immune tolerance against SE36 protein. Thus lower immune response may result in a limited genetic polymorphism of SE36.

About Malaria Vaccine Development

  • Fig. 1. Clinical trial of the NPC-SE36 malaria vaccine.
    The vaccine was produced under GMP (Good Manufacturing Practice) conditions at the Kanonji Institute of The Research Foundation for Microbial Diseases of Osaka University.
    (NPC-SE36 malaria vaccine was previously called BK-SE36 malaria vaccine.)

  • Fig. 2. Protective efficacy of NPC-SE36 malaria vaccine
    Palacpac et al., Plos ONE. 2013; 8(5): e64073

Staff

  • Endowed Chair Prof. : Toshihiro Horii
  • SA Prof. : Nirianne Marie Querijero Palacpac

Website

Publications

  • (1)African-specific polymorphisms in Plasmodium falciparum serine repeat antigen 5 in Uganda and Burkina Faso clinical samples do not interfere with antibody response to BK-SE36 vaccination. Arisue N, et al., Front Cell Infect Microbiol. (2022) 12:1058081. doi: 10.3389/fcimb.2022.1058081.
    (2)Safety and immunogenicity of BK-SE36 in a blinded, randomized, controlled, age de-escalating phase Ib clinical trial in Burkinabe children. Bougouma EC, et al., Front Immunol. (2022) 13:978591. doi: 10.3389/fimmu.2022.978591.
    (3)First-in-human randomized trial and follow-up study of Plasmodium falciparum blood-stage malaria vaccine BK-SE36 with CpG-ODN(K3) Ezoe S. et al., Vaccine (2020), S0264-410X(20)31227-5
    (4) Molecular Camouflage of Plasmodium falciparum Merozoites by Binding of Host Vitronectin to P47 Fragment of SERA5. Tougan T., et al., Sci Rep. (2018) 8:5052. doi: (5)10.1038/s41598-018-23194-9.
    (5) Antibody titres and boosting after natural malaria infection in BK-SE36 vaccine responders during a follow-up study in Uganda. Yagi M., et al., Sci Rep. (2016) 6:34363. doi: 10.1038/srep34363.
    (6) Protective Epitopes of the Plasmodium falciparum SERA5 Malaria Vaccine Reside in Intrinsically Unstructured N-Terminal Repetitive Sequences.Yagi M., et al., PLoS One. (2014) 9:e98460. doi: 10.1371/journal.pone.0098460.
    (7) Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36. Palacpac N.M.Q., et al., PLoS ONE. (2013) 8: e64073. doi:10.1371/journal.pone.0064073
    (8)Plasmodium falciparum serine repeat antigen 5 (SE36) as a malaria vaccine candidate. Palacpac N.M., et al., Vaccine. (2011) 29:5837-45. doi: 10.1016/j.vaccine.2011.06.052.
    (9) Evidences of Protection Against Blood-stage Infection of Plasmodium falciparum by the Novel Protein Vaccine SE36. Horii T., et al., Parasitol. Int. (2010) 59:380-6. doi: 10.1016/j.parint.2010.05.002.

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