Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

Abstract

HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported S. aureus vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model. Results showed that HI-mediated protection was altered in response to different adjuvants. Using antisera from immunized mice, we identified seven B-cell immunodominant epitopes on Hla and IsdB, including 6 novel epitopes (Hla1-18, Hla84-101, Hla186-203, IsdB342-359, IsdB366-383, and IsdB384-401). The immunodominance of B-cell epitopes, total IgG titers and the levels of IFN-γ and IL-17A from mice immunized with HI plus different adjuvants were different from each other, which may explain the difference in protective immunity observed in each immunized group. Thus, our results indicate that adjuvants largely affected the immunodominance of epitopes and the protective efficacy of HI, which may guide further adjuvant screening for vaccine development and optimization.

Differences in HPV-specific antibody Fc-effector functions following Gardasil® and Cervarix® vaccination

“…Several studies have noted that some adjuvants are able to break immunodominance more effectively, driving epitope spreading, breadth, and durability 49,50 . In this context, several adjuvants have been shown to drive superior epitope targeting compared to alum [51][52][53] . Correlation analysis of IgG titers and Fc receptor binding for all four strains included in Gardasil® (Supplementary Fig.…”

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

“…The protective response induced by an antigen is largely mediated by its immunodominant epitopes [34], which has been proven in various viral infections, including in uenza virus [35], porcine epidemic diarrhea virus [36] and SARS-CoV-2 [37]. Immune responses induced by different immunodominant epitopes of the same antigen can result in different protective e cacies [11]. The results showed that RBD-mediated protection was altered in response to different adjuvants and immune routes.…”

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

“…The protective response induced by an antigen is largely mediated by its immunodominant epitopes [34], which has been proven in various viral infections, including in uenza virus [35], porcine epidemic diarrhea virus[36] and SARS-CoV-2 [37]. Immune responses induced by different immunodominant epitopes of the same antigen can result in different protective e cacies [11]. The results showed that RBD-mediated protection was altered in response to different adjuvants and immune routes.…”

“…Thus, it is pivotal to improve the immunogenicity of RBD for vaccine development. Previous studies have shown that both the vaccination strategy and adjuvants are crucial for enhancing the protective immune response [10], and adjuvants largely affect the immunodominance of epitopes and the protective e cacy of a given antigen [11]. In addition, SARS-CoV-2 infection is typically initiated from the mucosa of the respiratory tract.…”