ジャーナル: Cell Rep Med / 年: 2022 タイトル: Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. 著者: Guidenn Sulbaran / Pauline Maisonnasse / Axelle Amen / Gregory Effantin / Delphine Guilligay / Nathalie Dereuddre-Bosquet / Judith A Burger / Meliawati Poniman / Marloes Grobben / Marlyse ...著者: Guidenn Sulbaran / Pauline Maisonnasse / Axelle Amen / Gregory Effantin / Delphine Guilligay / Nathalie Dereuddre-Bosquet / Judith A Burger / Meliawati Poniman / Marloes Grobben / Marlyse Buisson / Sebastian Dergan Dylon / Thibaut Naninck / Julien Lemaître / Wesley Gros / Anne-Sophie Gallouët / Romain Marlin / Camille Bouillier / Vanessa Contreras / Francis Relouzat / Daphna Fenel / Michel Thepaut / Isabelle Bally / Nicole Thielens / Franck Fieschi / Guy Schoehn / Sylvie van der Werf / Marit J van Gils / Rogier W Sanders / Pascal Poignard / Roger Le Grand / Winfried Weissenhorn / 要旨: 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) ...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.