High yield production of norovirus GII.4 virus-like particles using silkworm pupae and evaluation of their protective immunogenicity

Akitsu Masuda, Jae Man Lee, Takeshi Miyata, Shintaro Sato, Atsushi Masuda, Masahiro Taniguchi, Ryosuke Fujita, Hiroshi Ushijima, Keisuke Morimoto, Takeru Ebihara, Masato Hino, Kohei Kakino, Hiroaki Mon, Takahiro Kusakabe

Research output: Contribution to journalArticlepeer-review

Abstract

Noroviruses (NoVs) are one of the major causes of acute viral gastroenteritis in humans. Virus-like particles (VLPs) without genomes that mimic the capsid structure of viruses are promising vaccine candidates for the prevention of NoVs infection. To produce large amounts of recombinant protein, including VLPs, the silkworm-expression vector system (silkworm-BEVS) is an efficient and powerful tool. In this study, we constructed a recombinant baculovirus that expresses VP1 protein, the major structural protein of NoV GII.4. Expression analysis showed that the baculovirus-infected silkworm pupae expressed NoV VP1 protein more efficiently than silkworm larval fat bodies. We obtained about 4.9 mg of purified NoV VP1 protein from only five silkworm pupae. The purified VP1 protein was confirmed by dynamic light scattering and electron microscopy to form VLPs of approximately 40 nm in diameter. Antisera from mice immunized with the antigen blocked NoV VLPs binding to histo-blood group antigens of pig gastric mucin and also blocked NoV infection in intestinal epithelial cells derived from human induced pluripotent stem (iPS) cells. Our findings demonstrated that NoV VLP eliciting protective antibodies could be obtained in milligram quantities from a few silkworm pupae using the silkworm-BEVS.

Original languageEnglish
Pages (from-to)766-777
Number of pages12
JournalVaccine
Volume41
Issue number3
DOIs
Publication statusPublished - Jan 16 2023

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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