tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Jan 24;3(2):100528.
doi: 10.1016/j.xcrm.2022.100528. eCollection 2022 Feb 15.
Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection
Guidenn Sulbaran[SUP] 1 [/SUP], Pauline Maisonnasse[SUP] 2 [/SUP], Axelle Amen[SUP] 1 [/SUP], Gregory Effantin[SUP] 1 [/SUP], Delphine Guilligay[SUP] 1 [/SUP], Nathalie Dereuddre-Bosquet[SUP] 2 [/SUP], Judith A Burger[SUP] 3 [/SUP], Meliawati Poniman[SUP] 3 [/SUP], Marloes Grobben[SUP] 3 [/SUP], Marlyse Buisson[SUP] 1 [/SUP], Sebastian Dergan Dylon[SUP] 1 [/SUP], Thibaut Naninck[SUP] 2 [/SUP], Julien Lemaître[SUP] 2 [/SUP], Wesley Gros[SUP] 2 [/SUP], Anne-Sophie Gallouët[SUP] 2 [/SUP], Romain Marlin[SUP] 2 [/SUP], Camille Bouillier[SUP] 2 [/SUP], Vanessa Contreras[SUP] 2 [/SUP], Francis Relouzat[SUP] 2 [/SUP], Daphna Fenel[SUP] 1 [/SUP], Michel Thepaut[SUP] 1 [/SUP], Isabelle Bally[SUP] 1 [/SUP], Nicole Thielens[SUP] 1 [/SUP], Franck Fieschi[SUP] 1 [/SUP], Guy Schoehn[SUP] 1 [/SUP], Sylvie van der Werf[SUP] 4 5 [/SUP], Marit J van Gils[SUP] 3 [/SUP], Rogier W Sanders[SUP] 3 6 [/SUP], Pascal Poignard[SUP] 1 [/SUP], Roger Le Grand[SUP] 2 [/SUP], Winfried Weissenhorn[SUP] 1 [/SUP]
Affiliations
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[SUP]+[/SUP]-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.
Keywords: B cells; COVID-19; S glycoprotein; SARS-CoV-2; antibodies; formaldehyde cross-linking; immunity; macaques; nanoparticles; protection.
. 2022 Jan 24;3(2):100528.
doi: 10.1016/j.xcrm.2022.100528. eCollection 2022 Feb 15.
Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection
Guidenn Sulbaran[SUP] 1 [/SUP], Pauline Maisonnasse[SUP] 2 [/SUP], Axelle Amen[SUP] 1 [/SUP], Gregory Effantin[SUP] 1 [/SUP], Delphine Guilligay[SUP] 1 [/SUP], Nathalie Dereuddre-Bosquet[SUP] 2 [/SUP], Judith A Burger[SUP] 3 [/SUP], Meliawati Poniman[SUP] 3 [/SUP], Marloes Grobben[SUP] 3 [/SUP], Marlyse Buisson[SUP] 1 [/SUP], Sebastian Dergan Dylon[SUP] 1 [/SUP], Thibaut Naninck[SUP] 2 [/SUP], Julien Lemaître[SUP] 2 [/SUP], Wesley Gros[SUP] 2 [/SUP], Anne-Sophie Gallouët[SUP] 2 [/SUP], Romain Marlin[SUP] 2 [/SUP], Camille Bouillier[SUP] 2 [/SUP], Vanessa Contreras[SUP] 2 [/SUP], Francis Relouzat[SUP] 2 [/SUP], Daphna Fenel[SUP] 1 [/SUP], Michel Thepaut[SUP] 1 [/SUP], Isabelle Bally[SUP] 1 [/SUP], Nicole Thielens[SUP] 1 [/SUP], Franck Fieschi[SUP] 1 [/SUP], Guy Schoehn[SUP] 1 [/SUP], Sylvie van der Werf[SUP] 4 5 [/SUP], Marit J van Gils[SUP] 3 [/SUP], Rogier W Sanders[SUP] 3 6 [/SUP], Pascal Poignard[SUP] 1 [/SUP], Roger Le Grand[SUP] 2 [/SUP], Winfried Weissenhorn[SUP] 1 [/SUP]
Affiliations
- PMID: 35233549
- PMCID: PMC8784613
- DOI: 10.1016/j.xcrm.2022.100528
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[SUP]+[/SUP]-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.
Keywords: B cells; COVID-19; S glycoprotein; SARS-CoV-2; antibodies; formaldehyde cross-linking; immunity; macaques; nanoparticles; protection.