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Low-dose self-amplifying mRNA COVID-19 vaccine drives strong protective immunity in non-human primates against SARS-CoV-2 infection

Author

Listed:
  • Amy R. Rappaport

    (Gritstone bio, Inc.)

  • Sue-Jean Hong

    (Gritstone bio, Inc.)

  • Ciaran D. Scallan

    (Gritstone bio, Inc.)

  • Leonid Gitlin

    (Gritstone bio, Inc.)

  • Arvin Akoopie

    (Gritstone bio, Inc.)

  • Gregory R. Boucher

    (Gritstone bio, Inc.)

  • Milana Egorova

    (Gritstone bio, Inc.)

  • J. Aaron Espinosa

    (Gritstone bio, Inc.)

  • Mario Fidanza

    (Gritstone bio, Inc.)

  • Melissa A. Kachura

    (Gritstone bio, Inc.)

  • Annie Shen

    (Gritstone bio, Inc.)

  • Gloria Sivko

    (Battelle Biomedical Research Center)

  • Anne Abbema

    (Gritstone bio, Inc.)

  • Robert L. Veres

    (Gritstone bio, Inc.)

  • Karin Jooss

    (Gritstone bio, Inc.)

Abstract

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate strong cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 μg induced potent neutralizing antibody (nAb) titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 μg dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera. Spike-specific T cell responses were observed with all tested vaccine regimens. SAM vaccination provided protective efficacy against SARS-CoV-2 challenge as both a homologous prime-boost and as a single boost following ChAd prime, demonstrating reduction of viral replication in both the upper and lower airways. The SAM vaccine is currently being evaluated in clinical trials as both a homologous prime-boost regimen at low doses and as a boost following heterologous prime.

Suggested Citation

  • Amy R. Rappaport & Sue-Jean Hong & Ciaran D. Scallan & Leonid Gitlin & Arvin Akoopie & Gregory R. Boucher & Milana Egorova & J. Aaron Espinosa & Mario Fidanza & Melissa A. Kachura & Annie Shen & Glori, 2022. "Low-dose self-amplifying mRNA COVID-19 vaccine drives strong protective immunity in non-human primates against SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31005-z
    DOI: 10.1038/s41467-022-31005-z
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    Cited by:

    1. Christine D. Palmer & Ciaran D. Scallan & Lauren D. Kraemer Tardif & Melissa A. Kachura & Amy R. Rappaport & Daniel O. Koralek & Alison Uriel & Leonid Gitlin & Joshua Klein & Matthew J. Davis & Harshn, 2023. "GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. 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.
    3. Marco Mandolesi & Hrishikesh Das & Liset Vries & Yiqiu Yang & Changil Kim & Manojj Dhinakaran & Xaquin Castro Dopico & Julian Fischbach & Sungyong Kim & Mariia V. Guryleva & Monika Àdori & Mark Cherny, 2024. "Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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