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saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern

Author

Listed:
  • Mai Komori

    (VLP Therapeutics)

  • Takuto Nogimori

    (National Institutes of Biomedical Innovation, Health, and Nutrition)

  • Amber L. Morey

    (VLP Therapeutics)

  • Takashi Sekida

    (VLP Therapeutics Japan)

  • Keiko Ishimoto

    (VLP Therapeutics)

  • Matthew R. Hassett

    (VLP Therapeutics)

  • Yuji Masuta

    (National Institutes of Biomedical Innovation, Health, and Nutrition)

  • Hirotaka Ode

    (National Hospital Organization Nagoya Medical Center)

  • Tomokazu Tamura

    (Hokkaido University)

  • Rigel Suzuki

    (Hokkaido University)

  • Jeff Alexander

    (VLP Therapeutics)

  • Yasutoshi Kido

    (Osaka Metropolitan University)

  • Kenta Matsuda

    (VLP Therapeutics)

  • Takasuke Fukuhara

    (Hokkaido University)

  • Yasumasa Iwatani

    (National Hospital Organization Nagoya Medical Center
    Nagoya University Graduate School of Medicine)

  • Takuya Yamamoto

    (National Institutes of Biomedical Innovation, Health, and Nutrition
    Osaka University
    Osaka University)

  • Jonathan F. Smith

    (VLP Therapeutics)

  • Wataru Akahata

    (VLP Therapeutics Japan)

Abstract

Several vaccines have been widely used to counteract the global pandemic caused by SARS-CoV-2. However, due to the rapid emergence of SARS-CoV-2 variants of concern (VOCs), further development of vaccines that confer broad and longer-lasting protection against emerging VOCs are needed. Here, we report the immunological characteristics of a self-amplifying RNA (saRNA) vaccine expressing the SARS-CoV-2 Spike (S) receptor binding domain (RBD), which is membrane-anchored by fusing with an N-terminal signal sequence and a C-terminal transmembrane domain (RBD-TM). Immunization with saRNA RBD-TM delivered in lipid nanoparticles (LNP) efficiently induces T-cell and B-cell responses in non-human primates (NHPs). In addition, immunized hamsters and NHPs are protected against SARS-CoV-2 challenge. Importantly, RBD-specific antibodies against VOCs are maintained for at least 12 months in NHPs. These findings suggest that this saRNA platform expressing RBD-TM will be a useful vaccine candidate inducing durable immunity against emerging SARS-CoV-2 strains.

Suggested Citation

  • Mai Komori & Takuto Nogimori & Amber L. Morey & Takashi Sekida & Keiko Ishimoto & Matthew R. Hassett & Yuji Masuta & Hirotaka Ode & Tomokazu Tamura & Rigel Suzuki & Jeff Alexander & Yasutoshi Kido & K, 2023. "saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38457-x
    DOI: 10.1038/s41467-023-38457-x
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    References listed on IDEAS

    as
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    1. Nhân Thị Hồ & Steven G. Hughes & Van Thanh Ta & Lân Trọng Phan & Quyết Đỗ & Thượng Vũ Nguyễn & Anh Thị Văn Phạm & Mai Thị Ngọc Đặng & Lượng Viết Nguyễn & Quang Vinh Trịnh & Hùng Ngọc Phạm & Mến Văn Ch, 2024. "Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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