Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques.
Romain MarlinVeronique GodotSylvain CardinaudMathilde GalhautSeverin ColeonSandra ZurawskiNathalie BosquetMariangela CavarelliAnne-Sophie GallouëtPauline MaisonnasseLéa DupatyCraig FenwickThibaut NaninckJulien LemaitreMario Gomez-PachecoNidhal KahlaouiVanessa ContrerasFrancis RelouzatRaphaël Ho Tsong FangZhiqing WangJerome EllisCatherine ChaponMireille CentlivreAurélie WiedemannChristine LacabaratzMathieu SurenaudInga SzurgotPeter LiljeströmDelphine PlanasTimothee BruelOlivier SchwartzSylvie van der WerfGuiseppe PantaleoMélanie PragueRodolphe ThiebautGerard ZurawskiYves LévyRoger Le GrandPublished in: Nature communications (2021)
Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- induced apoptosis
- pregnant women
- high dose
- binding protein
- mouse model
- cancer therapy
- cell cycle arrest
- low dose
- healthcare
- early stage
- nk cells
- dendritic cells
- signaling pathway
- transcription factor
- endoplasmic reticulum stress
- cell proliferation
- stem cell transplantation
- dna methylation
- dna binding
- quantum dots
- working memory
- coronavirus disease
- monoclonal antibody