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Background: Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis. [ABSTRACT FROM AUTHOR]

Simple Summary: Streptococcus suis is an important bacterial pathogen, causing meningitis, arthritis, and endocarditis in pigs. Infections caused by S. suis lead to significant economic losses in the pig industry worldwide. The increasing prevalence of antimicrobial resistance (AMR), resulting in heightened global regulations on antibiotic use in livestock, has highlighted the critical need for alternative S. suis control strategies, such as vaccination. In the present study, we evaluated the protective effect of a subunit protein-based vaccine, targeting the phosphate ABC transporter ATP-binding protein (PstB) of S. suis serotype 2. PstB was shown to be highly conserved across various S. suis isolates. In mice, a candidate vaccine targeting the PstB protein induced the production of high levels of cytokines IFN-γ and IL-4, both considered to be important for protection against S. suis. Furthermore, the PstB-based vaccine was shown to provide a high level of (87.5%) protection against S. suis serotypes 2 and 9, with lower protection (62.5%) against S. suis serotype 7. These data indicate that PstB is a promising target antigen for development as a universal subunit vaccine against different S. suis serotypes. Streptococcus suis is a significant pathogen in pigs and a newly emerging zoonotic agent in humans. The presence of multiple serotypes and strains with diversified sequence types in pig herds highlights the need for the identification of broadly cross-reactive universal vaccine antigen targets, capable of providing cross-protection against S. suis infection. Subunit vaccines based on the conserved proteins shared between different S. suis serotypes are potential candidates for such a universally protective vaccine. In the present study, phosphate ABC transporter ATP-binding protein PstB (PstB), an immunogenic protein of the S. suis bacterium, was expressed and purified, and then subjected to cross-protection evaluation in mice. The PstB protein showed nearly 100% amino acid similarity across a panel of 31 S. suis isolates representing different serotypes, which were collected from different countries. A recombinant PstB (rPstB) protein (S. suis serotype 2) was recognized by rabbit sera specific to this serotype, and induced high levels of IFN-γ and IL-4 in mice immunized with the recombinant protein. These cytokines are considered important for protection against S. suis infection. Immunization of mice with rPstB resulted in an 87.5% protection against challenge with S. suis serotype 2 and 9 strains, suggesting a high level of cross-protection for S. suis serotypes 2 and 9. A lower protection rate (62.5%) was observed in mice challenged with the S. suis serotype 7 strain. These data demonstrate that PstB is a promising target antigen for development as a component of a universal subunit vaccine against multiple S. suis serotypes. [ABSTRACT FROM AUTHOR]

Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetella pertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation. [ABSTRACT FROM AUTHOR]

The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its -10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection., (© 2014 Crown copyright 2014. Reproduced with the permission of the controller of Her Majesty's Stationery Office/Queen's Printer for Scotland and Public Health England.)