Persistent Zika virus infection in porcine conceptuses is associated with elevated in utero cortisol levels

Persistent Zika virus infection in porcine conceptuses is associated with elevated <i>in utero</i> cortisol level

CIFSRF final technical report: development of a subunit vaccine for contagious bovine pleuropneumonia in Africa (CIFSRF Phase 2)

In Phase 1 we developed and patented three prototype vaccines, which protected animals challenged with the CBPP infectious agent. In Phase II of this project, we evaluated formulations of the experimental vaccine, tested and selected vaccine adjuvants, constructed vectors and strains for industrial production, and compared the new vaccine formulation to the existing vaccine using animal trials. The two most prevalent cattle breeds in East Africa,- Boran and Zebu were used in the animal trials. The project also supported transition to manufacturing of the vaccine at the Kenya Veterinary Vaccine Production Institute. A socio-economic program integrated at the beginning of the project addressed aspects of disease impact and vaccine adoption in support of a product rollout.This work was carried out with the aid of a grant from Canada’s International Development Research Centre (IDRC), and with financial support from the Government of Canada, provided through Global Affairs Canada (GAC)In support of transition to manufacturing, the team developed and tested vaccine formulations, aiming at selection of most effective protection, accompanied with reduction of production costs. Another step towards manufacturing was the execution of a license agreement by the three IP holder institutions and the vaccine manufacturer. The focal point of the socio-economic team was the economic impact of Contagious Bovine Pleuropneumonia (CBPP) and the potential of the new vaccine to reduce it. The report provides details of the milestones in the development, field trials, results and production of the vaccine

Commensal Bacteria and Expression of Two Major Intestinal Chemokines, TECK/CCL25 and MEC/CCL28, and Their Receptors

Background: CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. Their receptors, CCR9 and CCR10, are mainly expressed on T and B lymphocytes. In human, mouse, pig and sheep CCL25 and CCL28 play an important role in the segregation and the compartmentalization of the mucosal immune system. As evidenced by early comparisons of germ-free and conventional animals, the intestinal bacterial microflora has a marked effect on host intestinal immune functions. However, little is known about the impact of bacterial colonization on constitutive and induced chemokine expressions as well as on the generation of anti-inflammatory mechanisms. [br/] Methodology/Principal Findings: Therefore, we decided to focus by qPCR on the mRNA expression of two main gut chemokines, CCL25 and CCL28, their receptors CCR9 and CCR10, the Tregs marker Foxp3 and anti-inflammatory cytokines TGF-beta and IL-10 following colonization with different bacterial species within the small intestine. To accomplish this we used an original germ-free neonatal pig model and monoassociated pigs with a representative Gram-negative (Escherichia coli) or Gram-positive (Lactobacillus fermentum) commensal bacteria commonly isolated from the neonatal pig intestine. Our results show a consistent and marked effect of microbial colonization on the mRNA expression of intestinal chemokines, chemokine receptors, Foxp3 and TGF-beta. Moreover, as evidenced by in vitro experiments using two different cell lines, the pattern of regulation of CCL25 and CCL28 expression in the gut appears complex and suggests an additional role for in vivo factors. [br/] Conclusions/Significance: Taken together, the results highlight the key role of bacterial microflora in the development of a functional intestinal immune system in an elegant and relevant model for human immune system development

Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops

Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3×108 cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer’s patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer’s patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections

Neonatal pigs are susceptible to experimental Zika virus infection

Emerging Microbes & Infections (2017) 6, e6; doi:10.1038/emi.2016.133; published online 15 February 201

Experimental evaluation of inactivated and live attenuated vaccines against Mycoplasma mycoides subsp. mycoides

AbstractThe current control method for contagious bovine pleuropneumonia (CBPP) in Africa is vaccination with a live, attenuated strain of Mycoplasma mycoides subsp. mycoides (Mmm). However, this method is not very efficient and often causes serious adverse reactions. Several studies have attempted to induce protection using inactivated mycoplasma, but with widely contradictory results. Therefore, we compared the protective capacity of the live T1/44 vaccine with two inactivated preparations of Mmm strain Afadé, inoculated with an adjuvant. Protection was measured after a challenge with Afadé. The protection levels were 31%, 80.8% and 74.1% for the formalin-inactivated, heat-inactivated and live attenuated preparations, respectively. These findings indicate that low doses of heat-inactivated Mmm can offer protection to a level similar to the current live attenuated (T1/44) vaccine formulation

Animal board invited review: Risks of zoonotic disease emergence at the interface of wildlife and livestock systems.

The ongoing coronavirus disease 19s pandemic has yet again demonstrated the importance of the human-animal interface in the emergence of zoonotic diseases, and in particular the role of wildlife and livestock species as potential hosts and virus reservoirs. As most diseases emerge out of the human-animal interface, a better understanding of the specific drivers and mechanisms involved is crucial to prepare for future disease outbreaks. Interactions between wildlife and livestock systems contribute to the emergence of zoonotic diseases, especially in the face of globalization, habitat fragmentation and destruction and climate change. As several groups of viruses and bacteria are more likely to emerge, we focus on pathogenic viruses of the Bunyavirales, Coronaviridae, Flaviviridae, Orthomyxoviridae, and Paramyxoviridae, as well as bacterial species including Mycobacterium sp., Brucella sp., Bacillus anthracis and Coxiella burnetii. Noteworthy, it was difficult to predict the drivers of disease emergence in the past, even for well-known pathogens. Thus, an improved surveillance in hotspot areas and the availability of fast, effective, and adaptable control measures would definitely contribute to preparedness. We here propose strategies to mitigate the risk of emergence and/or re-emergence of prioritized pathogens to prevent future epidemics