Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine
Séverin Coléon
(1)
,
Aurélie Wiedemann
(1)
,
Mathieu Surénaud
(1)
,
Christine Lacabaratz
(1)
,
Sophie Hue
(1, 2)
,
Mélanie Prague
(3, 1)
,
Minerva Cervantes-Gonzalez
(4, 5)
,
Zhiqing Wang
(1, 6)
,
Jerome Ellis
(1, 6)
,
Amandine Sansoni
(7)
,
Camille Pierini
(7)
,
Quentin Bardin
(7)
,
Manon Fabregue
(7)
,
Sarah Sharkaoui
(7)
,
Philippe Hoest
(7)
,
Léa Dupaty
(1)
,
Florence Picard
(1)
,
Marwa El Hajj
(1)
,
Mireille Centlivre
(1)
,
Jade Ghosn
(5, 8)
,
Rodolphe Thiébaut
(3, 1)
,
Sylvain Cardinaud
(1)
,
Bernard Malissen
(7, 9)
,
Gérard Zurawski
(1, 6)
,
Ana Zarubica
(7)
,
Sandra Zurawski
(1, 6)
,
Véronique Godot
(1)
,
Yves Lévy
(1, 10)
1
VRI -
Vaccine Research Institute [Créteil, France]
2 Hôpital Henri Mondor
3 SISTM - Statistics In System biology and Translational Medicine
4 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
5 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
6 Baylor Scott & White Charles A. Sammons Cancer Center [Dallas, TX, USA]
7 CIPHE - Centre d'Immunophénomique
8 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
9 CIML - Centre d'Immunologie de Marseille - Luminy
10 Groupe Henri Mondor-Albert Chenevier
2 Hôpital Henri Mondor
3 SISTM - Statistics In System biology and Translational Medicine
4 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
5 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
6 Baylor Scott & White Charles A. Sammons Cancer Center [Dallas, TX, USA]
7 CIPHE - Centre d'Immunophénomique
8 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
9 CIML - Centre d'Immunologie de Marseille - Luminy
10 Groupe Henri Mondor-Albert Chenevier
Aurélie Wiedemann
- Fonction : Auteur
- PersonId : 759951
- ORCID : 0000-0002-4224-3137
Christine Lacabaratz
- Fonction : Auteur
- PersonId : 757905
- ORCID : 0000-0001-6925-0225
Mélanie Prague
- Fonction : Auteur
- PersonId : 11146
- IdHAL : mprague
- ORCID : 0000-0001-9809-7848
- IdRef : 175063427
Jerome Ellis
- Fonction : Auteur
- PersonId : 818372
- ORCID : 0000-0001-5224-3889
Mireille Centlivre
- Fonction : Auteur
- PersonId : 755800
- ORCID : 0000-0001-7616-9775
Jade Ghosn
- Fonction : Auteur
- PersonId : 765906
- ORCID : 0000-0003-2914-959X
Rodolphe Thiébaut
- Fonction : Auteur
- PersonId : 175125
- IdHAL : rodolphe-thiebaut
- ORCID : 0000-0002-5235-3962
- IdRef : 071580735
Sylvain Cardinaud
- Fonction : Auteur
- PersonId : 762692
- ORCID : 0000-0002-2650-1108
- IdRef : 259870595
Bernard Malissen
- Fonction : Auteur
- PersonId : 807282
- ORCID : 0000-0003-1340-9342
Ana Zarubica
- Fonction : Auteur
- PersonId : 758389
- ORCID : 0000-0001-5488-4137
Sandra Zurawski
- Fonction : Auteur
- PersonId : 765664
- ORCID : 0000-0002-8867-3765
Véronique Godot
- Fonction : Auteur
- PersonId : 756834
- ORCID : 0000-0003-3557-308X
Yves Lévy
- Fonction : Auteur
- PersonId : 759951
- ORCID : 0000-0002-4224-3137
Résumé
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).