Abstract
Streptococcus suis is a zoonotic pathogen affecting pigs and humans. This bacterium causes severe economic losses in the swine industry and poses a serious threat to public health and food safety. There is no effective commercial vaccine available for pigs or humans. In this study, we applied the biopolymer particle (BP) vaccine technology to incorporate seven conserved S. suis antigens (38 kDa protein (38), enolase (Enol), SSU1915, SSU1355, SSU0185, SSU1215, and SSU1773 (SSU1 and SSU2)). Two combinations of these antigens (38 and Enol; all SSU antigens designated as SSU1 and SSU2) were engineered to mediate production of BPs coated with either antigens 38 and Enol or SSU1 and SSU2 inside recombinant Escherichia coli. The isolated and purified empty BPs, 38-BP-Enol and SSU1-BP-SSU2, showed size ranges of 312–428 nm and 292–344 nm with and without the QuilA® adjuvant, respectively, and all showed a negative surface charge. Further characterization of purified BPs confirmed the presence of the expected antigen-comprising fusion proteins as assessed by tryptic peptide fingerprinting analysis using quadrupole time-of-flight mass spectrometry and immunoblotting. Vaccination with 38-BP-Enol and SSU1-BP-SSU2 formulated with and without QuilA® adjuvant induced significant antigen-specific humoral immune responses in mice. Antigen-coated BPs induced significant and specific Ig (IgM + IgG) and IgG immune responses (1.0 × 106–1.0 × 107) when compared with mice vaccinated with empty BPs. Functionality of the immune response was confirmed in challenge experiments using an acute murine S. suis infection model, which showed 100% survival of the 38-BP-Enol and SSU1-BP-SSU2 vaccinated mice compared to 70% survival when vaccinated with empty BPs. Overall, our data suggest that S. suis antigen-coated BPs could be developed into particulate vaccines that induce protective immunity against S. suis infections.
Highlights
Streptococcus suis is a Gram-positive bacterium and the major bacterial pathogen in pigs leading to significant economic losses to the swine industry worldwide
We developed S. suis particulate vaccine candidates applying the biopolymer particle (BP) vaccine technology that harnesses the capability of the bacteria to produce protein-coated BP inclusions [16,19]
This study suggests that the BP vaccine technology can be adapted for design and manufacture of particulate subunit vaccines that might protect against S. suis infection
Summary
Streptococcus suis is a Gram-positive bacterium and the major bacterial pathogen in pigs leading to significant economic losses to the swine industry worldwide. Meningitis is the most important clinical feature linked to S. suis infection in pigs. S. suis is a zoonotic pathogen that can be transmitted to humans. The infection caused by S. suis usually causes meningitis and endocarditis, cellulitis, peritonitis, and arthritis [4]. S. suis has become the most usual cause of human meningitis in Vietnam, second in Thailand, and third in Hong Kong. Asian countries are at risk of S. suis infections, while in Western countries it is considered as an occupational disease [3,4,5,6]. S. suis is undoubtedly posing a threat to public health and food safety and is considered as an emerging human pathogen [7]
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