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bioRxiv · 10.1101/320036

Baculovirus-inducing fast-acting innate immunity kills Plasmodium liver stages

Emran, T. B.·Iyori, M.·Ono, Y.·Amelia, F.·Yusuf, Y.·Islam, A.·Alam, A.·Ogawa, R.·Matsuoka, H.·Yamamoto, D.·Yoshida, S.
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Abstract

Baculovirus (BV), an enveloped insect virus with a circular double-stranded DNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. Here, we show that BV administration not only sterilely protects BALB/c mice for at least 7 days from subsequent Plasmodium berghei sporozoite infection but also eliminates existing liver-stage parasites completely, effects superior to those of primaquine, and does so in a TLR9-independent manner. Six hours post-BV administration, IFN- and IFN-{gamma} were robustly produced in serum, and RNA transcripts of interferon-stimulated genes were drastically upregulated in the liver. The in vivo passive transfer of post-BV administration serum effectively eliminated liver-stage parasites, and IFN- neutralization abolished this effect, indicating that the BV liver-stage parasite killing mechanism is downstream of the type I IFN signaling pathway. Our results demonstrate that BV is a potent IFN-inducing prophylactic and therapeutic agent with great potential for further development as a new malaria vaccine and/or anti-hypnozoite drug.

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Emran, T. B., Iyori, M., Ono, Y., Amelia, F., Yusuf, Y., Islam, A., Alam, A., Ogawa, R., Matsuoka, H., Yamamoto, D., Yoshida, S.. 2018-05-11. Baculovirus-inducing fast-acting innate immunity kills Plasmodium liver stages. https://doi.org/10.1101/320036

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