TLR4 Agonist Combined with Trivalent Protein JointS of Streptococcus suis Provides Immunological Protection in Animals.

Zhaofei Wang,Yuqiang Cheng,Mengting Guo,Licheng Kong,Jingjiao Ma,Ya Gao,Henan Wang,Jianhe Sun,Yaxian Yan

doi:10.3390/vaccines9020184

Abstract

Streptococcus suis (S. suis) serotype 2 (SS2) is the causative agent of swine streptococcosis and can cause severe diseases in both pigs and humans. Although the traditional inactive vaccine can protect pigs from SS2 infection, novel vaccine candidates are needed to overcome its shortcomings. Three infection-associated proteins in S. suis—muramidase-released protein (MRP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and DLD, a novel putative dihydrolipoamide dehydrogenase—have been previously identified by immunoproteomic assays. In this study, the effective immune protection of the recombinant trivalent protein GAPDH-MRP-DLD (JointS) against SS2, SS7, and SS9 was determined in zebrafish. To improve the immune efficacy of JointS, monophosphoryl lipid A (MPLA) as a TLR4 agonist adjuvant, which induces a strong innate immune response in the immune cells of mice and pigs, was combined with JointS to immunize the mice. The results showed that immunized mice could induce the production of a high titer of anti-S. suis antibodies; as a result, 100% of mice survived after SS2 infection. Furthermore, JointS provides good protection against virulent SS2 strain infections in piglets. Given the above, there is potential to develop JointS as a novel subunit vaccine for piglets to prevent infection by SS2 and other S. suis serotypes.

Highlights

Streptococcus suis (S. suis) is an important invasive swine pathogen associated with a wide range of diseases in pigs, including septicemia, pneumonia, meningitis, endocarditis, and arthritis [1,2,3]
The bacterial burden, which was given as the number of colony forming units (CFU) of S. suis, was measured in Todd Hewitt broth (THB) agar supplemented by 5%
The cloning, prokaryotic expression, and purification of glyceraldehyde-3phosphate dehydrogenase (GAPDH), muramidase-released protein (MRP), dihydrolipoamide dehydrogenase (DLD), and JointS were conducted as described in the Materials and Methods section

Summary

Introduction

Streptococcus suis (S. suis) is an important invasive swine pathogen associated with a wide range of diseases in pigs, including septicemia, pneumonia, meningitis, endocarditis, and arthritis [1,2,3]. 35 serotypes (types 1 to 34 and 1/2) have been identified on the basis of their capsular polysaccharides. Serotype 2 (SS2) is the most pathogenic and prevalent type in diseased pigs in most countries [4,5]. In 1998 and 2005, the cases of human SS2 infection with clinical signs of disease of streptococcal toxic shock syndrome (STSS) were reported in China, resulting in 14 and 38 human deaths, respectively [6,7]. It is necessary and extremely important to advance work in the prevention and control of SS2 infections

Methods

Results

Conclusion