Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

Refining the DC-targeting vaccination for preventing emerging infectious diseases

“…A recent work showed that an anti-CD40 antibody fused to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein induced significant levels of specific T- and B-cells, with a long-term memory phenotype in a humanized mouse model and the recall of neutralizing antibodies in SARS-CoV-2-convalescent non-human primates after one single dose of the vaccine administered without adjuvants ( 66 ). Finally, our lab showed that the fusion of CD40 targeting vaccine to a new generation of B- and T-cell epitopes from Spike and Nucleocapsid viral proteins of SARS-CoV-2 elicited high levels of cross-neutralizing antibodies against different variants in mice, as well as functional and specific T-cells responses in vitro ( 104 ).…”

“…Researchers must select suitable prediction tools that best adapt their objectives. Different studies used this reverse vaccinology strategy in order to select the best in-class epitopes for different infectious diseases such as SARS-CoV-2 ( 104 ), Nipah virus ( 130 ), Leishmania ( 131 ), HBV ( 132 ), HIV ( 133 ), Influenza ( 134 ), Tuberculosis ( 135 ), Ebola virus ( 136 ), Neisseria ( 137 ), Plasmodium ( 138 ), Trypanosoma ( 139 ), or Chikungunya and Mayaro viruses ( 140 ).…”

“…Time being the crucial factor, epitope-based peptide vaccines or recombinant vaccines might be a very helpful solution. Different studies have been accomplished for the prediction of B and T-cell epitopes, including a recent work from our group, in the context of the development of a Pan sarbecovirus anti-CD40 targeted vaccine candidate against multiple variants of concern of the SARS-CoV-2 ( 104 ) ( Figure 3 ).…”

“…(B) Example of the design of the Pan sarbecovirus anti-CD40 targeted vaccine after epitope mapping strategy. (C) CD40.CoV-2 vaccine construct, adapted from ( 104 ).…”

“…Therefore, the development of in silico antigen processing programs is an important tool to control the overall antigenicity of the vaccine construct. During the last decade, our group identified linker peptides with low immunogenicity and demonstrated that they were not interfering with the C-I or C-II antigen presentation of the viral peptides included within the DC-vaccine ( 99 , 104 ).…”