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Mind the gaps in research on the control of gastrointestinal nematodes of farmed ruminants and pigs.Transboundary and Emerging Diseases May 2018Gastrointestinal (GI) nematode control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health... (Review)
Review
Gastrointestinal (GI) nematode control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health and welfare. In this synthetic review, we identify key research priorities for GI nematode control in farmed ruminants and pigs, to support the development of roadmaps and strategic research agendas by governments, industry and policymakers. These priorities were derived from the DISCONTOOLS gap analysis for nematodes and follow-up discussions within the recently formed Livestock Helminth Research Alliance (LiHRA). In the face of ongoing spread of anthelmintic resistance (AR), we are increasingly faced with a failure of existing control methods against GI nematodes. Effective vaccines against GI nematodes are generally not available, and anthelmintic treatment will therefore remain a cornerstone for their effective control. At the same time, consumers and producers are increasingly concerned with environmental issues associated with chemical parasite control. To address current challenges in GI nematode control, it is crucial to deepen our insights into diverse aspects of epidemiology, AR, host immune mechanisms and the socio-psychological aspects of nematode control. This will enhance the development, and subsequent uptake, of the new diagnostics, vaccines, pharma-/nutraceuticals, control methods and decision support tools required to respond to the spread of AR and the shifting epidemiology of GI nematodes in response to climatic, land-use and farm husbandry changes. More emphasis needs to be placed on the upfront evaluation of the economic value of these innovations as well as the socio-psychological aspects to prioritize research and facilitate uptake of innovations in practice. Finally, targeted regulatory guidance is needed to create an innovation-supportive environment for industries and to accelerate the access to market of new control tools.
Topics: Animals; Animals, Domestic; Anthelmintics; Biomedical Research; Communicable Disease Control; Gastrointestinal Diseases; Livestock; Nematoda; Nematode Infections; Protozoan Vaccines; Ruminants; Swine; Swine Diseases
PubMed: 29124904
DOI: 10.1111/tbed.12707 -
Methods in Molecular Biology (Clifton,... 2022Giardia lamblia is the only known parasite that can inhabit the harsh upper gastrointestinal tract, where most of the digestive proteases are secreted. Intestinal and...
Giardia lamblia is the only known parasite that can inhabit the harsh upper gastrointestinal tract, where most of the digestive proteases are secreted. Intestinal and free-living protozoa express surface proteins containing an extraordinarily high percentage of cysteine. These cysteine-rich variant-specific surface proteins (VSPs) form a dense coat on the entire surface of Giardia trophozoites, that coat protects the parasite inside the host intestine. VSPs not only are resistant to proteolytic digestion, extreme pH and temperatures, but also stimulate host immune responses. These properties can be used to protect as well as to increase the immunogenicity of vaccine antigens for oral administration. The incorporation of VSPs onto virus-like particles bearing viral antigens allows oral administration of these vaccines, protecting the antigens from degradation and generating robust and protective immune responses. In this chapter we describe the development of this versatile vaccine platform for the generation of safe, stable, and efficient oral vaccines, including their production and validation, as well as the characterization of immune response to oral immunization.
Topics: Administration, Oral; Antigens, Protozoan; Cysteine; Membrane Proteins; Protozoan Proteins; Protozoan Vaccines; Vaccines
PubMed: 34914065
DOI: 10.1007/978-1-0716-1884-4_26 -
Poultry Science Mar 2021A series of studies was conducted to determine the effects of a quillaja and yucca (saponin) combination (QY) product on postvaccination oocyst production, development... (Meta-Analysis)
Meta-Analysis
Concurrent use of saponins and live coccidiosis vaccines: the influence of a quillaja and yucca combination on anticoccidial effects and performance results of coccidia-vaccinated broilers.
A series of studies was conducted to determine the effects of a quillaja and yucca (saponin) combination (QY) product on postvaccination oocyst production, development of coccidial immunity, and final bird performance of broilers administered live coccidiosis vaccines. In all, 3 groups of tests were carried out. Study 1 evaluated the effects of QY (0 and 250 ppm) on oocyst per gram of feces (OPG) following vaccination at day-of-age; OPG were measured from 5 to 12 d postvaccination. Study 2 determined the effects of QY (250 ppm) in the presence of 3 commercial coccidiosis vaccines in floor pens. OPG were measured weekly for birds receiving each vaccine and for each corresponding vaccine group fed QY. To determine whether QY influenced the development of coccidial immunity induced by the 3 vaccines, 5 birds were removed from each pen at 28 d and challenged with pathogenic levels of Eimeria spp. At 6 d post challenge, lesion scores were used to evaluate the effects of QY on immune protection provided by each vaccine. In addition, comparisons of final bird performance were made between birds given each vaccine and their corresponding vaccinates fed QY. Study 3 comprised a meta-analysis of 15 floor pen trials in which 21- and 42-d body weight, feed conversions, and total mortality were compared between coccidiosis-vaccinated broilers and similarly vaccinated broilers fed QY (250 ppm). Results of these experiments indicated that feeding QY to vaccinated broilers did not significantly affect OPG from days 5 through 12 postvaccination (P > 0.05). For each vaccine tested in study 2, OPG values were the highest at 14 and 21 d postvaccination. QY significantly reduced OPG at 14 d postvaccination for 2 of the vaccines tested, and produced a similar effect in 1 vaccine at 21 d postvaccination. The remaining vaccine was not affected by QY in the postvaccination OPG results. Despite these changes in OPG, significant differences in lesion scores following the Eimeria challenge were not observed for any vaccinated groups receiving QY. Irrespective of the vaccine, both interim and final feed conversion values were significantly improved when QY was fed (P < 0.01). Similarly, results of a 15-trial meta-analysis indicated that QY-fed vaccinated broilers had higher body weights, improved feed conversions, and lower mortality than their vaccinated controls. Results show that while QY may induce changes in OPG following vaccination, coccidia-vaccinated broilers fed QY develop immunity equivalent to that of controls and show significant improvements in performance and mortality.
Topics: Animal Feed; Animals; Chickens; Coccidiosis; Poultry Diseases; Protozoan Vaccines; Quillaja; Saponins; Yucca
PubMed: 33518338
DOI: 10.1016/j.psj.2020.12.010 -
Vaccine Jun 2019The knowledge that the immune system is composed of a regulatory/suppressor arm added a new point of view to better understand the nature of several pathologies... (Review)
Review
The knowledge that the immune system is composed of a regulatory/suppressor arm added a new point of view to better understand the nature of several pathologies including cancer, transplants, infections and autoimmune diseases. The striking discoveries concerning molecules and cells involved in this kind of regulation were followed by the elucidation of equally notable mechanisms used by several pathogens to manipulate the host immune system. Vaccines against pathogens are an invaluable tool developed to help the immune system cope with a potential infection or prevent disease pathology. Nowadays, there is accumulated evidence indicating that the powerful stimulation capacity of vaccines influences not only the effector arm of the immune system but also cells with regulatory/suppressor capacity, such as myeloid derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs). Trypanosoma cruzi (T. cruzi) is a protozoan parasite with a complex life cycle that has evolved several strategies to influence the regulatory immune response. Although diverse vaccine formulations have been able to stimulate the effector response, achieving non-sterilizing protection against T. cruzi, the influence of the vaccine candidates on the regulatory machinery has scarcely been assessed. This fact may not only reveal important information concerning how vaccines may influence cells with regulatory/suppressor capacity but also open the possibility to analyze whether vaccines are able to disrupt the mechanisms used by some pathogens to manipulate the host regulatory circuits. The aim of this review is to summarize and discuss available data related to the role of cellular components, like MDSCs and Foxp3+ Tregs, during T. cruzi infection, and the potential utility of those populations as additional targets for the rational design of vaccines.
Topics: Animals; Antigens, Protozoan; Chagas Disease; Humans; Immune System; Protozoan Vaccines; Trypanosoma cruzi; Vaccination
PubMed: 31155420
DOI: 10.1016/j.vaccine.2019.05.015 -
International Maritime Health 2019The authors present a short summary of the current state of malaria vaccine development and the per- spectives for the availability of a malaria vaccines for travellers...
The authors present a short summary of the current state of malaria vaccine development and the per- spectives for the availability of a malaria vaccines for travellers from non-endemic countries. There is currently no commercially available malaria vaccine for travellers. The efficacy of the RTS,S/AS01 vaccine is limited and differs dramatically from the effects of other vaccines administered in travel medicine. In the current recommendations, the use of repellents is deemed the most important measure to prevent malaria infection, and in the high-risk destinations, chemoprophylaxis is strongly advised. Many questions in malaria vaccinology remain unanswered.
Topics: Humans; Malaria; Malaria Vaccines; Plasmodium; Travel-Related Illness
PubMed: 30931520
DOI: 10.5603/IMH.2019.0010 -
Frontiers in Immunology 2022Cheap, easy-to-produce oral vaccines are needed for control of coccidiosis in chickens to reduce the impact of this disease on welfare and economic performance. yeast...
Cheap, easy-to-produce oral vaccines are needed for control of coccidiosis in chickens to reduce the impact of this disease on welfare and economic performance. yeast expressing three antigens were developed and delivered as heat-killed, freeze-dried whole yeast oral vaccines to chickens in four separate studies. After vaccination, replication was reduced following low dose challenge (250 oocysts) in Hy-Line Brown layer chickens (p<0.01). Similarly, caecal lesion score was reduced in Hy-Line Brown layer chickens vaccinated using a mixture of S. cerevisiae expressing EtAMA1, EtIMP1 and EtMIC3 following pathogenic-level challenge (4,000 oocysts; p<0.01). Mean body weight gain post-challenge with 15,000 oocysts was significantly increased in vaccinated Cobb500 broiler chickens compared to mock-vaccinated controls (p<0.01). Thus, inactivated recombinant yeast vaccines offer cost-effective and scalable opportunities for control of coccidiosis, with relevance to broiler production and chickens reared in low-and middle-income countries (LMICs).
Topics: Animals; Chickens; Coccidiosis; Eimeria tenella; Female; Male; Poultry Diseases; Protozoan Proteins; Protozoan Vaccines; Saccharomyces cerevisiae; Vaccination; Vaccines, Subunit
PubMed: 35185896
DOI: 10.3389/fimmu.2022.809711 -
Frontiers in Immunology 2022Toxoplasmosis is a worldwide disease affecting all warm-blooded animals, including humans. Vaccination strategies aimed at inducing an efficient immune response while...
Toxoplasmosis is a worldwide disease affecting all warm-blooded animals, including humans. Vaccination strategies aimed at inducing an efficient immune response while preventing transmission have been attempted in the past. While many different approaches can partially protect immunized animals against subsequent infections, full and lasting protection is rarely attained and only with live-attenuated vaccines. In addition, vaccines based on mutant strains that are deficient in forming the chronic phase of the parasite (such as Toxovax™) cannot be extensively used due to their zoonotic potential and the possibility of reversion to virulent phenotypes. An increasing number of studies using emerging genetic-engineering tools have been conducted to design novel vaccines based on recombinant proteins, DNA or delivery systems such as nanoparticles. However, these are usually less efficient due to their antigenic simplicity. In this perspective article we discuss potential target genes and novel strategies to generate live-attenuated long-lasting vaccines based on tissue cysts and oocysts, which are the environmentally resistant chronic forms of . By selectively disrupting genes important for parasite dissemination, cyst formation and/or sporozoite invasion, alone or in combination, a vaccine based on a live-attenuated strain that elicits a protective immune response while preventing the transmission of could be created. Finally, further improvements of protocols to generate sexual stages might lead to the production of oocysts from such a strain without the need for using mice or cats.
Topics: Animals; Cysts; Mice; Oocysts; Protozoan Vaccines; Toxoplasma; Toxoplasmosis, Animal; Vaccines, Attenuated
PubMed: 35734184
DOI: 10.3389/fimmu.2022.910961 -
International Journal of Biological... Oct 2016Amoebiasis/amebiasis is a gastrointestinal infection caused by an enteric dwelling protozoan, Entamoeba histolytica. The disease is endemic in the developing world and... (Review)
Review
Amoebiasis/amebiasis is a gastrointestinal infection caused by an enteric dwelling protozoan, Entamoeba histolytica. The disease is endemic in the developing world and is transmitted mainly via the faecal-oral route (e.g., in water or food) and may or may not be symptomatic. This disease of socio-economic importance worldwide involves parasite adherence and cytolysis of human cells followed by invasion that is mediated by galactose-binding (Gal/GalNAc) surface lectin. Disruption of the mucus layer leads to invasive intestinal and extraintestinal infection. Gal-lectin based vaccinations have conferred protection in various animal models against E. histolytica infections. Keeping in view the pivotal role of Gal/GalNAc lectin in amoebiasis vaccine development, its regulation, genomic view of the parasite involving gene conversion in lectin gene families, current knowledge about involvement of Gal/GalNAc lectin in adherence, pathogenicity, signalling, encystment, generating host immune response, and in turn protozoa escape strategies, and finally its role as effective vaccine candidate has been described. This review will help researchers to explore pathogenesis mechanism along with genomic studies and will also provide a framework for future amoebiasis vaccine development studies.
Topics: Animals; Entamoeba histolytica; Entamoebiasis; Galectins; Humans; Protozoan Proteins; Protozoan Vaccines
PubMed: 27181579
DOI: 10.1016/j.ijbiomac.2016.05.043 -
The Journal of Parasitology Nov 2021Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of... (Review)
Review
Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of foodborne illness-related death. Currently, there exists no approved vaccine for humans or most livestock against the parasite. DNA vaccines, a type of subunit vaccine which uses segments of the pathogen's DNA to generate immunity, have shown varying degrees of experimental efficacy against infection caused by the parasite. This review compiles DNA vaccine efforts against Toxoplasma gondii, segmenting the analysis by parasite antigen, as well as a review of concomitant adjuvant usage. No single antigenic group was consistently more effective within in vivo trials relative to others.
Topics: Adjuvants, Immunologic; Animals; Antigens, Protozoan; Humans; Microneme; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccines, DNA
PubMed: 34852176
DOI: 10.1645/20-157 -
Frontiers in Immunology 2023, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective...
, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from , was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti--specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce -specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after challenge ( 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively ( 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against infection.
Topics: Animals; Mice; Mice, Inbred BALB C; Protozoan Proteins; Protozoan Vaccines; Toxoplasmosis; Immunization; Immunoglobulin G
PubMed: 37122740
DOI: 10.3389/fimmu.2023.1161507