Host-adapted Gram-negative bacterial pathogens from the Pasteurellaceae , Neisseriaceae , and Moraxellaceae families normally reside in the upper respiratory or genitourinary tracts of their hosts and rely on utilizing iron from host transferrin (Tf) for growth and survival. The surface receptor proteins that mediate this critical iron acquisition pathway have been proposed as ideal vaccine targets due to the critical role that they play in survival and disease pathogenesis in vivo . In particular, the surface lipoprotein component of the receptor, Tf binding protein B (TbpB), had received considerable attention as a potential antigen for vaccines in humans and food production animals but this has not translated into the series of successful vaccine products originally envisioned. Preliminary immunization experiments suggesting that host Tf could interfere with development of the immune response prompted us to directly address this question with site-directed mutant proteins defective in binding Tf. Site-directed mutants with dramatically reduced binding of porcine transferrin and nearly identical structure to the native proteins were prepared. A mutant Haemophilus parasuis TbpB was shown to induce an enhanced B-cell and T-cell response in pigs relative to native TbpB and provide superior protection from infection than the native TbpB or a commercial vaccine product. The results indicate that binding of host transferrin modulates the development of the immune response against TbpBs and that strategies designed to reduce or eliminate binding can be used to generate superior antigens for vaccines.
A set of 207 Streptococcus suis isolates were collected from ten autonomous communities from Spain in 2019 to 2020 from pigs with meningitis, pneumonic lungs, arthritic joints or other swollen viscera, to a lesser extent. Thirteen capsular types were detected being the most prevalent serotype 2 (21.7%), followed by serotypes 1 (21.3%), 9 (19.3%) and 3 (6.3%). Serotypes 2 and 9 were recovered mainly from the central nervous system (CNS), while serotype 1 was isolated mostly from swollen joints and serotype 3 from the lungs. Twenty-five isolates (12.1%) could not be typed. The most prevalent pathotype was epf + mrp + sly + luxS (49 isolates, 23.8%), and it was related mainly to serotypes 1 and 2. Serotypes 1–3 and 9 were significantly associated with anatomical sites of isolation and virulence factors, serotype 9 (CNS) and serotypes 3 and 9 (lungs) being associated with virulence profiles without the epf gene. S. suis isolates showed globally high antimicrobial resistances, but ampicillin followed by spectinomycin and tiamulin resulted in the highest activities, while the greatest resistances were detected for sulphadimethoxine, tetracyclines, neomycin, clindamycin and macrolides. A total of 87.4% isolates were positive to the tetO gene, 62.4% to the ermB gene and 25.2% to the fexA gene, while 14.6% were positive to all three genes simultaneously. A significative association between isolate resistances to tetracyclines and macrolides and the resistance genes tested was established, except for phenicol resistance and the fexA gene. A set of 14 multiresistance patterns were obtained according to the number of antimicrobials to which the isolates were resistant, the resistances to 12 or more agents being the most prevalent ones. A remarkable amount of multiresistance profiles could be seen among the S. suis serotype 9 isolates.
Haemophilus parasuisis the agent responsible for causing Glässer's disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis in pigs. In this study, we have characterized native outer membrane proteins with affinity to porcine transferrin (NPAPT) fromH. parasuisserovar 5, Nagasaki strain. This pool of proteins was used as antigen to developed two vaccine formulations: one was adjuvanted with a mineral oil (Montanide IMS 2215 VG PR), while the other was potentiated with a bacterial neuraminidase fromClostridium perfringens. The potential protective effect conferred by these two vaccines was compared to that afforded by two other vaccines, consisting of recombinant transferrin-binding protein (rTbp) A or B fragments fromH. parasuis, Nagasaki strain, and by a commercially available inactivated vaccine. Five groups of colostrum-deprived piglets immunized with the vaccines described above, one group per each vaccine, and a group of nonvaccinated control animals were challenged intratracheally with a lethal dose (3 × 108CFU) ofH. parasuis, Nagasaki strain. The two vaccines containing rTbps yielded similar results with minimal protection against death, clinical signs, gross and microscopic lesions, andH. parasuisinvasion. In contrast, the two vaccines composed of NPAPT antigen and commercial bacterin resulted in a strong protection against challenge (without deaths and clinical signs), mild histopathological changes, and no recovery ofH. parasuis, thus suggesting their effectiveness in preventing Glässer's disease outbreaks caused by serovar 5.