Cell Reports Medicine (Apr 2021)

SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses

  • Marco Mandolesi,
  • Daniel J. Sheward,
  • Leo Hanke,
  • Junjie Ma,
  • Pradeepa Pushparaj,
  • Laura Perez Vidakovics,
  • Changil Kim,
  • Monika Àdori,
  • Klara Lenart,
  • Karin Loré,
  • Xaquin Castro Dopico,
  • Jonathan M. Coquet,
  • Gerald M. McInerney,
  • Gunilla B. Karlsson Hedestam,
  • Ben Murrell

Journal volume & issue
Vol. 2, no. 4
p. 100252

Abstract

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Summary: The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

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