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 SERA5
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 developed malaria vaccine NPC-SE36 by utilizing a recombinant SE36 protein. SE36 is a protein that is highly expressed/produced in large amounts during parasite growth in red blood cells. Epidemiological studies in malaria hyper-endemic areas showed that children with antibodies against SERA5 experienced few or no symptomatic/clinical malaria, albeit such children are a minority.
It was surprising that Ugandan adults that suffered numerous malaria infections did not respond to vaccination with BK-SE36. By contrast, malaria-naïve 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 Ib trial. This suggests that our vaccine provides better protection in younger individuals. We have conducted Phase Ib 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 2-5 years child group. Currently we are conducting Phase Ib clinical trial of NPC-SE36 with CpG adjuvant that stimulates innate immunity.
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, SERA5 is highly homologous among malaria parasites worldwide. We have analyzed protective epitopes on SE36 protein. 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.
- Endowed Chair Prof. : Toshihiro Horii
- SA Prof. : Nirianne Marie Querijero Palacpac
- (1) 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.
(2) 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.
(3) 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.
(4) 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
(5) 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.
(6) 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.