The Pneumococcal Polysaccharide-Tetanus Toxin Native C-Fragment Conjugate Vaccine: The Carrier Effect and Immunogenicity.

Rui Yu,Junjie Xu,Wei Chen,Tao Hu

doi:10.1155/2020/9596129

Abstract

The encapsulated bacteria, as Streptococcus pneumonia, Haemophilus influenzae type b, and Neisseria meningitidis, cause serious morbidity and mortality worldwide. The capsular polysaccharide (PS), which could elicit a weak T cell-independent immune response, is a vital virulence determinant. One of the strategies to improve the PS-specific immunogenicity is to conjugate PS with a nontoxic carrier protein. Tetanus toxoid (TT) and CRM197 are the typical carrier proteins for the PS conjugate vaccines. TT is the inactivated tetanus toxin manipulated with formaldehyde, which suffers from the pollution from residual formaldehyde and the incomplete detoxification. CRM197 has the disadvantage of low-yield purification with the requirement of sophisticated culture conditions. Thus, a novel carrier protein without these disadvantages is highly required. The tetanus toxin native C-fragment (Hc) is safe, low-cost, and highly immunogenic with easy purification, which can act as a promising carrier protein. Pneumococcal serogroups 14 and 23F were major epidemic causes of pneumococcal infections. In the present study, the capsular PSs (PS14 and PS23F) were conjugated with Hc, TT, and CRM197, respectively. TT- and CRM197-based conjugates acted as controls for Hc-based conjugates (PS14-Hc and PS23F-Hc). The structural properties of Hc were not fundamentally changed after conjugated with PS. PS14-Hc and PS23F-Hc could potentiate sound PS-specific antibody levels comparable to the controls. Thus, Hc exhibited a practical carrier effect to help the pneumococcal conjugate vaccines perform good immunogenicities.

Highlights

The encapsulated bacteria with capsular polysaccharide (PS), as Streptococcus pneumonia, Haemophilus influenzae type b, and Neisseria meningitidis, cause serious morbidity and mortality worldwide [1]
PS14-Tetanus toxoid (TT) was first eluted as a significant peak at 45.2 ml, followed by a small peak of the unconjugated TT (Figure 2(c))
The reaction mixture containing PS23F-TT was eluted as a single peak at 42.4 ml (Figure 2(f))

Summary

Introduction

The encapsulated bacteria with capsular polysaccharide (PS), as Streptococcus pneumonia, Haemophilus influenzae type b, and Neisseria meningitidis, cause serious morbidity and mortality worldwide [1]. The PS vaccines elicit weak T cell-independent immune responses without long-term immunological memories, in children and the old [6, 7]. The conjugate vaccines have been produced by covalent conjugation of the antigenic PS with a nontoxic carrier protein to enhance the immunogenicity of PS vaccines [8,9,10]. After priming with the carrier protein, the immune response of PS improved by increasing the number of T lymphocytes [11, 12]. The carrier protein can anchor PS to the B cell MHC-II, which makes the carbohydrate moiety present to T cell and eliciting T cell-dependent response to PS [13, 14]. The conjugate vaccines have been demonstrated to be immunogenic and capable of inducing immunological memory and high avidity [15]

Methods

Results

Conclusion