Distinct immunological features of Ferritin and AP205 nanovaccines lead to differing therapeutic outcomes against chronic hepatitis B

Ferritin and AP205 are two well-established representative nanoparticle platforms widely used in vaccine development. However, their immunological properties, vaccine efficacy, and underlying mechanisms remain incompletely characterized. In this study, we systematically compared the immune profiles of Ferritin- and AP205-based nanovaccines, explored their mechanisms of action, and evaluated their efficiency in the AAV-HBV infection mouse model. Our results demonstrated that the AP205 vaccine, which incorporates intrinsic ssRNA as a built-in adjuvant, elicited a stronger antibody response with a balanced IgG1/IgG2c profile. In contrast, the Ferritin vaccine supplemented with extrinsic CpG adjuvant induced an IgG1-biased antibody response. At the T cell level, the AP205 vaccine promoted a more mature germinal center T follicular helper (GC-Tfh) cell response, whereas the Ferritin+CpG vaccine stimulated a stronger Th1 response, likely due to enhanced dendritic cell activation by CpG. We further showed that codelivery of antigen and adjuvant is necessary and sufficient to augment IgG2c response for both platforms. Functionally, although the AP205-preS1 vaccine exhibited superior preventive efficacy against acute AAV-HBV infection compared to the Ferritin-preS1 +CpG vaccine, it showed reduced therapeutic efficacy against chronic AAV-HBV infection, highlighting the importance of Th1 immunity in viral clearance. Together, these findings suggest that the AP205 platform may serve as an effective platform for prophylactic vaccines, while Ferritin+CpG may hold greater potential for therapeutic applications requiring strong Th1 responses, such as chronic hepatitis B (CHB).