CD20-Mimotope Peptides: A Model to Define the Molecular Basis of Epitope Spreading

Abstract

Antigen-mimicking peptide (mimotope)-based vaccines are one of the most promising forms of active-immunotherapy. The main drawback of this approach is that it induces antibodies that react poorly with the nominal antigen. The aim of this study was to investigate the molecular basis underlying the weak antibody response induced against the naïve protein after peptide vaccination. For this purpose, we analyzed the fine specificity of monoclonal antibodies (mAb) elicited with a 13-mer linear peptide, complementary to theantigen-combining site of the anti-CD20 mAb, Rituximab, in BALB/c mice. Anti-peptide mAb competed with Rituximab for peptide binding. Even so, they recognized a different antigenic motif from the one recognized by Rituximab. This explains their lack of reactivity with membrane (naïve) CD20. These data indicate that even on a short peptide the immunogenic and antigenic motifs may be different. These findings highlight an additional mechanism for epitope spreading and should be taken into account when designing peptides for vaccine purposes.

Peptides, Antibodies, Peptide Antibodies and More

“…Thus, even though the synthetic peptides induce Abs, they are not necessarily reactive with the target antigen, which testifies to the very high specificity of Abs. The same applies to putative mimotopes of CD20, which may be identified by phage display screening for CD20 epitopes/mimotopes, but do not elicit CD20 cross-reactive Abs upon immunization [145], which, again, demonstrates the very high specificity of (peptide) Abs.…”

“…Rituximab targets an epitope on the extracellular domain of CD20, which is a prominent B cell antigen, and is an attractive target for a peptide vaccine inducing CD20 Abs. However, despite several attempts, no such vaccine has been successful as described by Favoino et al in this issue [145]. One of the problems with this approach is that it is difficult with a synthetic peptide to mimic the three-dimensional structure of native membrane-bound CD20.…”

Mimotope discovery as a tool to design a vaccine against Zika and dengue viruses

“…Also, mimotopes have been reported to induce antibodies to other immunogenic motifs, masking the response to the desired epitope, a phenomenon known as epitope spreading (Favoino et al, 2019).…”

Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens

“…Thus, the biopanning process of phage display toward monoclonal as well as polyclonal antibodies (Abs) could be performed to detect TAA mimotopes. 81,82 A better solution is to produce anti-TAA Abs continuously and endogenously in a process called active vaccination. It aims both to eliminate cancer and to decrease the risk of recurrence.…”

“…In one such concept, tumor‐associated antigens (TAAs) are considered as rational targets for cancer treatment. Thus, the biopanning process of phage display toward monoclonal as well as polyclonal antibodies (Abs) could be performed to detect TAA mimotopes 81,82 . A better solution is to produce anti‐TAA Abs continuously and endogenously in a process called active vaccination.…”