Fitri Amelia, Mitsuhiro Iyori, Talha Bin Emran, Daisuke S. Yamamoto, Kento Genshi, Hiromu Otsuka, Yutaro Onoue, Yenni Yusuf, Ashekul Islam, Shigeto Yoshida
Plasmodium falciparum circumsporozoite protein (PfCSP) is the main target antigen in development of pre-erythrocytic malaria vaccines. To evaluate PfCSP vaccines in animal models, challenge by intravenous sporozoite injection is preferentially used. However, in clinical trials, vaccinated human volunteers are exposed to the bites of malaria-infected mosquitoes. In this study, we down-selected Escherichia coli-produced full-length PfCSP (PfCSP-F) and its three truncated PfCSPs based on their abilities to elicit immune response and protection in mice against two challenge models. We showed that immunization with three doses of PfCSP-F elicited high anti-PfCSP antibody titres and 100% protection against the bites of infected mosquitoes. Meanwhile, three-dose truncated PfCSP induced 60%-70% protection after immunization with each truncated PfCSP. Heterologous prime-boost immunization regimen with adenovirus-PfCSP-F and R32LR greatly induced complete protection against intravenous sporozoite injection. Our results suggest that Abs to both anti-repeat and anti-nonrepeat regions induced by PfCSP-F are required to confer complete protection against challenge by the bites of infected mosquitoes, whereas anti-repeat Abs play an important role in protection against intravenous sporozoite injection. Our findings provide a potential clinical application that PfCSP-F vaccine induces potent Abs capable of neutralizing sporozoites in the dermis inoculated by infected mosquitoes and subsequently sporozoites in the blood circulation. © 2019 John Wiley & Sons Ltd
Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Japan; Department of Chemistry, Universitas Negeri Padang, Padang, Indonesia; Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Shimotsuke, Japan
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