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

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 antibodie...

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Veröffentlicht in:Cell reports. Medicine 2021-04, Vol.2 (4), p.100252-100252, Article 100252
Hauptverfasser: Mandolesi, Marco, Sheward, Daniel J., Hanke, Leo, Ma, Junjie, Pushparaj, Pradeepa, Perez Vidakovics, Laura, Kim, Changil, Àdori, Monika, Lenart, Klara, Loré, Karin, Castro Dopico, Xaquin, Coquet, Jonathan M., McInerney, Gerald M., Karlsson Hedestam, Gunilla B., Murrell, Ben
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Sprache:eng
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Zusammenfassung: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. [Display omitted] Neutralizing antibodies are detectable after one adjuvanted spike protein immunizationBoosting yields higher neutralizing titers than observed in seropositive human donorsNeutralizing antibody titers remain high for at least 4 months after the last boostImmunization stimulates spike-specific memory B cells Mandolesi et al. show that immunization with adjuvanted prefusion-stabilized SARS-CoV-2 spike glycoprotein yields potent antibody responses in mice and macaques. Neutralizing antibodies are detectable after one immunization. Boosting results in exceptional potency, with neutralizing titers exceeding (>10-fold) those observed in seropositive humans and remaining high during a 4-month follow-up.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2021.100252