Infections caused by Streptococcus suis are considered a global and an economical problem in the swine industry. Moreover, S. suis is an agent of zoonosis that afflicts people in close contact with infected pigs or pork-derived products. Although sporadic cases of S. suis infections in humans (mainly meningitis) have been reported during the last 40 years, a large outbreak due to this pathogen emerged in the summer of 2005 in China. The severity of the infection in humans during the outbreak, such as a shorter incubation time, more rapid disease progression and higher rate of mortality, attracted a lot of attention from the scientific community and the general press. In fact, the number of publications on S. suis (including the number of reported human cases) has significantly increased during recent years. In this article we critically review the present knowledge on S. suis infection in humans, we discuss the hypotheses that may explain the 2005 outbreak and the repercussion of such an episode on the scientific community.

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Edited by Wilhelm JustInteractions between a bacterial pathogen and its potentially susceptible host are initiated with the colonization step. During respiratory/oral infection, the pathogens must compete with the normal microflora, resist defense mechanisms of the local mucosal immunity, and finally reach, adhere, and breach the mucosal epithelial cell barrier in order to induce invasive disease. This is the case during infection by the swine and zoonotic pathogen Streptococcus suis, which is able to counteract mucosal barriers to induce severe meningitis and sepsis in swine and in humans. The initial steps of the pathogenesis of S. suis infection has been a neglected area of research, overshadowed by studies on the systemic and central nervous phases of the disease. In this Review article, we provide for the first time, an exclusive focus on S. suis colonization and the potential mechanisms involved in S. suis establishment at the mucosa, as well as the mechanisms regulating mucosal barrier breakdown. The role of mucosal immunity is also addressed. Finally, we demystify the extensive list of putative adhesins and virulence factors reported to be involved in the initial steps of pathogenesis by S. suis.

Despite efforts made to develop efficient preventive strategies, infections with influenza A viruses (IAV) continue to cause serious clinical and economic problems. Current licensed human vaccines are mainly inactivated whole virus particles or split-virion administered via the parenteral route. These vaccines provide incomplete protection against IAV in high-risk groups and are poorly/not effective against the constant antigenic drift/shift occurring in circulating strains. Advances in mucosal vaccinology and in the understanding of the protective anti-influenza immune mechanisms suggest that intranasal immunization is a promising strategy to fight against IAV. To date, human mucosal anti-influenza vaccines consist of live attenuated strains administered intranasally, which elicit higher local humoral and cellular immune responses than conventional parenteral vaccines. However, because of inconsistent protective efficacy and safety concerns regarding the use of live viral strains, new vaccine candidates are urgently needed. To prime and induce potent and long-lived protective immune responses, mucosal vaccine formulations need to ensure the immunoavailability and the immunostimulating capacity of the vaccine antigen(s) at the mucosal surfaces, while being minimally reactogenic/toxic. The purpose of this review is to compile innovative delivery/adjuvant systems tested for intranasal administration of inactivated influenza vaccines, including micro/nanosized particulate carriers such as lipid-based particles, virus-like particles and polymers associated or not with immunopotentiatory molecules including microorganism-derived toxins, Toll-like receptor ligands and cytokines. The capacity of these vaccines to trigger specific mucosal and systemic humoral and cellular responses against IAV and their (cross)-protective potential are considered.

dStreptococcus suis serotype 2 is an encapsulated bacterium and one of the most important bacterial pathogens in the porcine industry. Despite decades of research for an efficient vaccine, none is currently available. Based on the success achieved with other encapsulated pathogens, a glycoconjugate vaccine strategy was selected to elicit opsonizing anti-capsular polysaccharide (anti-CPS) IgG antibodies. In this work, glycoconjugate prototypes were prepared by coupling S. suis type 2 CPS to tetanus toxoid, and the immunological features of the postconjugation preparations were evaluated in vivo. In mice, experiments evaluating three different adjuvants showed that CpG oligodeoxyribonucleotide (ODN) induces very low levels of anti-CPS IgM antibodies, while the emulsifying adjuvants Stimune and TiterMax Gold both induced high levels of IgGs and IgM. Dose-response trials comparing free CPS with the conjugate vaccine showed that free CPS is nonimmunogenic independently of the dose used, while 25 g of the conjugate preparation was optimal in inducing high levels of anti-CPS IgGs postboost. With an opsonophagocytosis assay using murine whole blood, sera from immunized mice showed functional activity. Finally, the conjugate vaccine showed immunogenicity and induced protection in a swine challenge model. When conjugated and administered with emulsifying adjuvants, S. suis type 2 CPS is able to induce potent IgM and isotype-switched IgGs in mice and pigs, yielding functional activity in vitro and protection against a lethal challenge in vivo, all features of a T cell-dependent response. This study represents a proof of concept for the potential of glycoconjugate vaccines in veterinary medicine applications against invasive bacterial infections.

bStreptococcus agalactiae (also known as group B Streptococcus [GBS]) and Streptococcus suis are encapsulated streptococci causing severe septicemia and meningitis. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. The mechanisms underlying anti-CPS antibody responses are not fully elucidated, but the biochemistry of CPSs, particularly the presence of sialic acid, may have an immunosuppressive effect. We investigated the ability of highly purified S. suis and GBS native (sialylated) CPSs to activate dendritic cells (DCs), which are crucial actors in the initiation of humoral immunity. The influence of CPS biochemistry was studied using CPSs extracted from different serotypes within these two streptococcal species, as well as desialylated CPSs. No interleukin-1␤ (IL-1␤), IL-6, IL-12p70, tumor necrosis factor alpha (TNF-␣), or IL-10 production was observed in S. suis or GBS CPS-stimulated DCs. Moreover, these CPSs exerted immunosuppressive effects on DC activation, as a diminution of gamma interferon (IFN-␥)-induced B cell-activating factor of the tumor necrosis factor family (BAFF) expression was observed in CPS-pretreated cells. However, S. suis and GBS CPSs induced significant production of CCL3, via partially Toll-like receptor 2 (TLR2)-and myeloid differentiation factor 88 (MyD88)-dependent pathways, and CCL2, via TLR-independent mechanisms. No major influence of CPS biochemistry was observed on the capacity to induce chemokine production by DCs, indicating that DCs respond to these CPSs in a patterned way rather than a structure-dedicated manner.

The capsular polysaccharide (CPS) of Streptococcus suis serotype 14 was purified, chemically modified, and characterized. Sugar and absolute configuration analyses gave the following CPS composition: D-Gal, 3; D-Glc, 1; D-GlcNAc, 1; D-Neu5Ac, 1. The Sambucus nigra lectin, which recognizes the Neu5Ac(α2-6)Gal/GalNAc sequence, showed binding to the native CPS. Sialic acid was found to be terminal, and the CPS was quantitatively desialylated by mild acid hydrolysis. It was also submitted to periodate oxidation followed by borohydride reduction and Smith degradation. Sugar and methylation analyses, (1)H and (13)C nuclear magnetic resonance, and mass spectrometry of the native CPS or of its specifically modified products allowed to determine the repeating unit sequence: [6)[Neu5Ac(α2-6)Gal(β1-4)GlcNAc(β1-3)]Gal(β1-3)Gal(β1-4)Glc(β1-](n). S. suis serotype 14 CPS has an identical sialic acid-containing side chain as serotype 2 CPS, but differs by the absence of rhamnose in its composition. The same side chain is also present in group B Streptococcus type Ia CPS, except that in the latter sialic acid is 2,3- rather than 2,6-linked to the following galactose. A correlation between the S. suis CPS sequence and genes of the serotype 14 cps locus encoding putative glycosyltransferases and polymerase responsible for the biosynthesis of the repeating unit is proposed.

bStreptococcus suis serotype 2 is an extracellular encapsulated bacterium that causes severe septicemia and meningitis in swine and humans. Albeit crucial in the fight against encapsulated bacteria, the nature of the capsular polysaccharide (CPS)-specific antibody (Ab) response during S. suis type 2 infection is unknown. We compared for the first time the features of CPS-specific versus protein-specific Ab responses during experimental infections with live virulent S. suis type 2 in mice. The primary protein-specific Ab response was dominated by both type 1 and 2 IgG subclasses, whereas IgM titers were more modest. The secondary protein-specific Ab response showed all of the features of a memory response with faster kinetics and boosted the titers of all Ig isotypes. In contrast, the primary CPS-specific Ab response was either inexistent or had titers only slightly higher than those in noninfected animals and was essentially composed of IgM. A poor CPS-specific memory response was observed, with only a moderate boost in IgM titers and no IgG. Both protein-and CPS-specific Ab responses were Toll-like receptor 2 independent. By using S. suis type 2 strains of European or North American origin, the poor CPS-specific Ab response was demonstrated to be independent of the genotypic/phenotypic diversity of the strain within serotype 2. Finally, the CPS-specific Ab response was also impaired and lacked isotype switching in S. suis-infected pigs, the natural host of the bacterium. The better resistance of preinfected animals to reinfection with the same strain of S. suis type 2 might thus more likely be related to the development of a protein rather than CPS Ab response.