tetano
Editor, Senior Moderator
EBioMedicine
. 2022 May 17;80:104062.
doi: 10.1016/j.ebiom.2022.104062. Online ahead of print.
Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine
Séverin Coléon[SUP] 1 [/SUP], Aurélie Wiedemann[SUP] 1 [/SUP], Mathieu Surénaud[SUP] 1 [/SUP], Christine Lacabaratz[SUP] 1 [/SUP], Sophie Hue[SUP] 2 [/SUP], Mélanie Prague[SUP] 3 [/SUP], Minerva Cervantes-Gonzalez[SUP] 4 [/SUP], Zhiqing Wang[SUP] 5 [/SUP], Jerome Ellis[SUP] 5 [/SUP], Amandine Sansoni[SUP] 6 [/SUP], Camille Pierini[SUP] 6 [/SUP], Quentin Bardin[SUP] 6 [/SUP], Manon Fabregue[SUP] 6 [/SUP], Sarah Sharkaoui[SUP] 6 [/SUP], Philippe Hoest[SUP] 6 [/SUP], Léa Dupaty[SUP] 1 [/SUP], Florence Picard[SUP] 1 [/SUP], Marwa El Hajj[SUP] 1 [/SUP], Mireille Centlivre[SUP] 1 [/SUP], Jade Ghosn[SUP] 7 [/SUP], French COVID Cohort Study Group; Rodolphe Thiébaut[SUP] 8 [/SUP], Sylvain Cardinaud[SUP] 1 [/SUP], Bernard Malissen[SUP] 9 [/SUP], Gérard Zurawski[SUP] 5 [/SUP], Ana Zarubica[SUP] 6 [/SUP], Sandra M Zurawski[SUP] 5 [/SUP], Véronique Godot[SUP] 1 [/SUP], Yves Lévy[SUP] 10 [/SUP]
Affiliations
Abstract
Background: There is an urgent need of a new generation of vaccine that are able to enhance protection against SARS-CoV-2 and related variants of concern (VOC) and emerging coronaviruses.
Methods: We identified conserved T- and B-cell epitopes from Spike (S) and Nucleocapsid (N) highly homologous to 38 sarbecoviruses, including SARS-CoV-2 VOCs, to design a protein subunit vaccine targeting antigens to Dendritic Cells (DC) via CD40 surface receptor (CD40.CoV2).
Findings: CD40.CoV2 immunization elicited high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with viral control and survival after SARS-CoV-2 challenge. A direct comparison of CD40.CoV2 with the mRNA BNT162b2 vaccine showed that the two vaccines were equally immunogenic in mice. We demonstrated the potency of CD40.CoV2 to recall in vitro human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes.
Interpretation: We report the immunogenicity and antiviral efficacy of the CD40.CoV2 vaccine in a preclinical model providing a framework for a pan-sarbecovirus vaccine.
Fundings: This work was supported by INSERM and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR and the CARE project funded from the Innovative Medicines Initiative 2 Joint Undertaking (JU).
Keywords: COVID-19; Pre-clinical model; SARS-CoV-2; Sarbecoviruses; Vaccine.
. 2022 May 17;80:104062.
doi: 10.1016/j.ebiom.2022.104062. Online ahead of print.
Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine
Séverin Coléon[SUP] 1 [/SUP], Aurélie Wiedemann[SUP] 1 [/SUP], Mathieu Surénaud[SUP] 1 [/SUP], Christine Lacabaratz[SUP] 1 [/SUP], Sophie Hue[SUP] 2 [/SUP], Mélanie Prague[SUP] 3 [/SUP], Minerva Cervantes-Gonzalez[SUP] 4 [/SUP], Zhiqing Wang[SUP] 5 [/SUP], Jerome Ellis[SUP] 5 [/SUP], Amandine Sansoni[SUP] 6 [/SUP], Camille Pierini[SUP] 6 [/SUP], Quentin Bardin[SUP] 6 [/SUP], Manon Fabregue[SUP] 6 [/SUP], Sarah Sharkaoui[SUP] 6 [/SUP], Philippe Hoest[SUP] 6 [/SUP], Léa Dupaty[SUP] 1 [/SUP], Florence Picard[SUP] 1 [/SUP], Marwa El Hajj[SUP] 1 [/SUP], Mireille Centlivre[SUP] 1 [/SUP], Jade Ghosn[SUP] 7 [/SUP], French COVID Cohort Study Group; Rodolphe Thiébaut[SUP] 8 [/SUP], Sylvain Cardinaud[SUP] 1 [/SUP], Bernard Malissen[SUP] 9 [/SUP], Gérard Zurawski[SUP] 5 [/SUP], Ana Zarubica[SUP] 6 [/SUP], Sandra M Zurawski[SUP] 5 [/SUP], Véronique Godot[SUP] 1 [/SUP], Yves Lévy[SUP] 10 [/SUP]
Affiliations
- PMID: 35594660
- DOI: 10.1016/j.ebiom.2022.104062
Abstract
Background: There is an urgent need of a new generation of vaccine that are able to enhance protection against SARS-CoV-2 and related variants of concern (VOC) and emerging coronaviruses.
Methods: We identified conserved T- and B-cell epitopes from Spike (S) and Nucleocapsid (N) highly homologous to 38 sarbecoviruses, including SARS-CoV-2 VOCs, to design a protein subunit vaccine targeting antigens to Dendritic Cells (DC) via CD40 surface receptor (CD40.CoV2).
Findings: CD40.CoV2 immunization elicited high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with viral control and survival after SARS-CoV-2 challenge. A direct comparison of CD40.CoV2 with the mRNA BNT162b2 vaccine showed that the two vaccines were equally immunogenic in mice. We demonstrated the potency of CD40.CoV2 to recall in vitro human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes.
Interpretation: We report the immunogenicity and antiviral efficacy of the CD40.CoV2 vaccine in a preclinical model providing a framework for a pan-sarbecovirus vaccine.
Fundings: This work was supported by INSERM and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR and the CARE project funded from the Innovative Medicines Initiative 2 Joint Undertaking (JU).
Keywords: COVID-19; Pre-clinical model; SARS-CoV-2; Sarbecoviruses; Vaccine.