Immunodominance of epitopes and protection efficacy of RBD antigen are differentially altered by different adjuvants and immune pathways

Abstract

Purpose Previous studies have revealed that the receptor-binding domain (RBD) of the spike protein is immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in RBD-mediated protection. In this study, we evaluated the immunodominant humoral response of RBD with different adjuvants and different immune routes in inducing neutralizing antibodies and immunodominant epitopes in RBD. Methods In this study, we investigated the protective efficacy of immunization with RBD plus three different adjuvants (Al(OH)3, ASO3 or AddaVax) and two different routes (intramuscular immunity or intranasal immunity) in a mouse model. Results The results showed that RBD-mediated protection was altered in response to different adjuvants; even with the same adjuvant, RBD-mediated protection was altered in different immune routes. Using antisera from immunized mice, we identified six B-cell immunodominant epitopes in the RBD, including 2 novel epitopes (RBD1 − 18 and RBD49 − 66) in intramuscular immunity and 3 novel epitopes (RBD31 − 48, RBD61 − 78, RBD97 − 114) in intranasal immunity. The B-cell immunodominant epitopes identified from mice immunized with RBD plus different adjuvants were also different from each other, which may explain the differences in protective immunity observed in each immunized group. Conclusions This study indicate that adjuvants and immune pathways largely affect the immunodominance of epitopes and the protective efficacy of RBD, which may guide further adjuvant screening for vaccine development and optimization.

Immunogenicity studies of recombinant RBD SARS-CoV-2 as a COVID-19 vaccine candidate produced in Escherichia coli

“…These epitopes notably contained immunodominant peptide sequences, “VRQIAP” and “YQAGSTP,” pivotal for eliciting the humoral immune response. Moreover, our work uncovered additional immunodominant epitopes, “VLYNSASFSTFKYGVSP” and “PFERISTEIYQAGSTPC,” reportedly influential in IgG response stimulation in BALB/c mice [23] .…”

“…Furthermore, we conducted an in silico study of rRBD epitopes against B cell receptors using immunoinformatic prediction Bepipred 2.0 on https://tools.iedb.org , seven of which could bind antibodies ( Figure S2 ). Jiang et al [22] and Li et al [23] demonstrated that the SARS-CoV-2 RBD epitopes “ATRFAS,” “YAWNRKRISN,” “DEVRQIAPGQTGKIADYNYK,” “STEIYQAGSTPCNGVE” [22] , as well as “VLYNSASFSTFKYGVSP” and “PFERISTEIYQAGSTPC” [23] are dominant and bind immunoglobulins (Ig).…”