Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection - Groupe Entrée et bourgeonnement des virus à enveloppe / Entry and Budding of Enveloped Viruses Group (EBEV)
Journal Articles Cell Reports Medicine Year : 2022

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection

Daphna Fenel
Michel Thepaut
Isabelle Bally
Nicole Thielens
Franck Fieschi
Guy Schoehn
Winfried Weissenhorn

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the "down" conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4+-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.
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hal-03621344 , version 1 (28-03-2022)

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Guidenn Sulbaran, Pauline Maisonnasse, Axelle Amen, Gregory Effantin, Delphine Guilligay, et al.. Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. Cell Reports Medicine, 2022, 3 (2), pp.100528. ⟨10.1016/j.xcrm.2022.100528⟩. ⟨hal-03621344⟩
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