Elicitation of integrated immunity in mice by a novel pneumococcal polysaccharide vaccine conjugated with HBV surface antigen

Wen Qian,Min Chen,Qihan Li,Yuqiu Chen,Zhen Huang,Kai Wu,Jing Shi,Yongzhong Duan,Nanping Chen,Jinling Yang,Ying Zhang,Lili Wang

doi:10.1038/s41598-020-62185-7

Abstract

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines. Therefore, the identification and optimization of carrier proteins to induce an effective immune response is necessary for developing a combined vaccine. In the current study, we utilized hepatitis B virus surface antigen (HBsAg) as a novel carrier protein combined with a capsular polysaccharide molecule to develop a new pneumococcal conjugated vaccine. The specific antibodies and T cell immune response against the capsular polysaccharide and HBsAg in the mice immunized with this conjugated vaccine were evaluated. In addition, the unique gene profiles of immune cells induced by this conjugated vaccine in the immunized mice were analyzed. Our results demonstrated that the vaccine consisting of pneumonia type 33 F capsular polysaccharide (Pn33Fps) conjugated with HBsAg can induce strong specific immune responses against both antigens in vivo in immunized mice. Furthermore, the conjugated vaccine induced higher expression of genes related to the activation of immunity and higher antibody titers against Pn33Fps and HBsAg in mice than those obtained via vaccination with a single antigen. Analyses of the dynamic expression changes in immunity-related genes in mice immunized with Pn33Fps_HBs, Pn33Fps, or HBsAg indicated the potent immunogenicity of the conjugated vaccine. In addition, a pathological evaluation of the organs from immunized mice further suggested that the conjugated vaccine is safe. Together, these results indicate that a conjugated vaccine consisting of Pn33Fps with HBsAg is a novel and effective vaccine.

Highlights

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines
Because the hepatitis B virus surface antigen (HBsAg) vaccine has been successfully applied in the Expanded Program of Immunization (EPI) and exhibits good clinical protective effectiveness and safety in children[24,25], the study described here investigated the hypothesis that hepatitis B surface antigen (HBsAg) might be a better carrier protein than other candidates for the development of pneumococcal conjugated vaccines
Compared with the serum samples collected at different time points from mice immunized with the carrier protein HBsAg (Fig. 1), serum collected from mice immunized with Pn33Fps_HBs showed higher GEMT titers of antibodies specific for HBsAg, whereas both groups exhibited similar seroconversion (Fig. 2a)

Summary

Introduction

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines. Because the HBsAg vaccine has been successfully applied in the Expanded Program of Immunization (EPI) and exhibits good clinical protective effectiveness and safety in children[24,25], the study described here investigated the hypothesis that hepatitis B surface antigen (HBsAg) might be a better carrier protein than other candidates for the development of pneumococcal conjugated vaccines. This hypothesized technical strategy leads to the design of a combined vaccine for the control of hepatitis B and pneumonia in the EPI because it could function with a new pneumococcal conjugated vaccine. The data obtained in this work support the technical strategy of using pneumococcal polysaccharide-conjugated vaccines depending on the HBsAg vaccine carrier protein

Methods

Results

Conclusion