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Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants

Author

Listed:
  • Charles B. Stauft

    (Food and Drug Administration)

  • Prabhuanand Selvaraj

    (Food and Drug Administration)

  • Felice D’Agnillo

    (Food and Drug Administration)

  • Clement A. Meseda

    (Food and Drug Administration)

  • Shufeng Liu

    (Food and Drug Administration)

  • Cyntia L. Pedro

    (Food and Drug Administration)

  • Kotou Sangare

    (Food and Drug Administration)

  • Christopher Z. Lien

    (Food and Drug Administration)

  • Jerry P. Weir

    (Food and Drug Administration)

  • Matthew F. Starost

    (National Institutes of Health)

  • Tony T. Wang

    (Food and Drug Administration)

Abstract

Detection of secretory antibodies in the airway is highly desirable when evaluating mucosal protection by vaccines against a respiratory virus, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that intranasal delivery of an attenuated SARS-CoV-2 (Nsp1-K164A/H165A) induces both mucosal and systemic IgA and IgG in male Syrian hamsters. Interestingly, either direct intranasal immunization or airborne transmission-mediated delivery of Nsp1-K164A/H165A in Syrian hamsters offers protection against heterologous challenge with variants of concern (VOCs) including Delta, Omicron BA.1, BA.2.12.1 and BA.5. Vaccinated animals show significant reduction in both tissue viral loads and lung inflammation. Similarly attenuated viruses bearing BA.1 and BA.5 spike boost variant-specific neutralizing antibodies in male mice that were first vaccinated with modified vaccinia virus Ankara vectors (MVA) expressing full-length WA1/2020 Spike protein. Together, these results demonstrate that our attenuated virus may be a promising nasal vaccine candidate for boosting mucosal immunity against future SARS-CoV-2 VOCs.

Suggested Citation

  • Charles B. Stauft & Prabhuanand Selvaraj & Felice D’Agnillo & Clement A. Meseda & Shufeng Liu & Cyntia L. Pedro & Kotou Sangare & Christopher Z. Lien & Jerry P. Weir & Matthew F. Starost & Tony T. Wan, 2023. "Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39090-4
    DOI: 10.1038/s41467-023-39090-4
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    1. Sandile Cele & Laurelle Jackson & David S. Khoury & Khadija Khan & Thandeka Moyo-Gwete & Houriiyah Tegally & James Emmanuel San & Deborah Cromer & Cathrine Scheepers & Daniel G. Amoako & Farina Karim , 2022. "Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization," Nature, Nature, vol. 602(7898), pages 654-656, February.
    2. Shufeng Liu & Charles B. Stauft & Prabhuanand Selvaraj & Prabha Chandrasekaran & Felice D’Agnillo & Chao-Kai Chou & Wells W. Wu & Christopher Z. Lien & Clement A. Meseda & Cyntia L. Pedro & Matthew F., 2022. "Intranasal delivery of a rationally attenuated SARS-CoV-2 is immunogenic and protective in Syrian hamsters," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Rigel Suzuki & Daichi Yamasoba & Izumi Kimura & Lei Wang & Mai Kishimoto & Jumpei Ito & Yuhei Morioka & Naganori Nao & Hesham Nasser & Keiya Uriu & Yusuke Kosugi & Masumi Tsuda & Yasuko Orba & Michihi, 2022. "Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant," Nature, Nature, vol. 603(7902), pages 700-705, March.
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