Single dose HBsAg CS-γ-PGA nanogels induce potent protective immune responses against HBV infection

Abstract

Hepatitis B virus (HBV) infection is a severe threat to public health, which can be prevented by prophylactic vaccination. Here, we tested nanogels carriers in the prophylactic effect of hepatitis B surface antigen (HBsAg) vaccine. HBsAg nanogels (Ng) were prepared using chitosan (CS) and poly-γ-glutamic acid (γ-PGA). Positively charged Ng (+) and negatively charged Ng (−) were prepared by adjusting the CS and γ-PGA proportion. Dendritic cells (DCs) maturation in mice immunized with HBsAg Ng (+) and HBsAg Ng (−) could be augmented in response to pAAV/HBV1.2 plasmid challenge. Single-dose immunization with HBsAg Ng (+) induced HBsAg specific-antibodies. HBsAg Ng (+) immunized mice cleared HBsAg and restored anti-HBs production after pAAV/HBV1.2 plasmid challenge. Single-dose HBsAg Ng (+) induced humoral and cellular immunity, and could induce effector memory T cells. Single-dose HBsAg Ng (−) favored the induction of cellular immunity, and induced central memory T cells and effector memory T cells. However, HBsAg elimination was similar between HBsAg Ng (+)- and HBsAg Ng (+) plus HBsAg Ng (−)-immunized mice. Zeta potential measurements showed that HBsAg Ng (+) were more stable than HBsAg Ng (−). Therefore, Ng (+) are desirable HBsAg prophylactic vaccine carriers, providing long-term protection against HBV, and are a good choice to study and apply weakly immunostimulatory antigens.