-
Revue Scientifique Et Technique... Aug 2015The Theileria genus includes a large number of species of tick-borne parasites that infect domestic animals and wildlife species, predominantly ruminants. These range... (Review)
Review
The Theileria genus includes a large number of species of tick-borne parasites that infect domestic animals and wildlife species, predominantly ruminants. These range from species, such as T. parva and T. annulata, which cause acute lymphoproliferative diseases in cattle resulting in high levels of mortality, to others that are non-pathogenic. In the last decade, several new pathogenic species of Theileria have been identified and pathogenic strains of other previously low-pathogenic species have emerged. Theileria parasites are characterised by developmental stages within leukocytes and erythrocytes. The capacity of the most pathogenic species to undergo extensive multiplication during intra-leukocyte development is central to their ability to cause disease. However, this is not the sole property responsible for disease, as illustrated by T. parva, which grows in a similar mannerin buffalo cells butdoes notcause disease inthisspecies. Because of the highly pathogenic nature of these parasites in livestock and the susceptibility of young animals to disease, control of the diseases is challenging. Control by chemotherapy and prevention of tick infestation has proved expensive and difficult to sustain. Vaccines using live parasites are available for T. parva and T. annulata and have been used with some success in the field. However, their widespread use has been hampered by practical constraints in production and distribution of the vaccines. Studies of the immune responses in immune cattle have helped to elucidate the protective immune responses and identified a number of parasite antigens that are currently being explored for development of alternative vaccines.
Topics: Animals; Animals, Domestic; Protozoan Vaccines; Theileriasis
PubMed: 26601460
DOI: 10.20506/rst.34.2.2383 -
Trends in Parasitology Mar 2019Important progress has been made in understanding how immunity is elicited against Toxoplasma gondii - a complex pathogen with multiple mechanisms of immune evasion.... (Review)
Review
Important progress has been made in understanding how immunity is elicited against Toxoplasma gondii - a complex pathogen with multiple mechanisms of immune evasion. Many vaccine candidates have been tested using various strategies in animal models. However, none of these strategies has delivered as yet, and important challenges remain in the development of vaccines that can eliminate the tissue cysts and/or fully block vertical transmission. In this review, we provide an overview of the current understanding of the host immune response to T. gondii infection and summarize the key limitations for the development of an effective, safe, and durable toxoplasmosis vaccine. We also discuss how the successes and failures in developing and testing vaccine candidates have provided a roadmap for future vaccine development.
Topics: Animals; Humans; Protozoan Vaccines; Research; Toxoplasma; Toxoplasmosis
PubMed: 30718083
DOI: 10.1016/j.pt.2019.01.005 -
Iranian Biomedical Journal Jan 2022Leishmaniasis is caused by protozoan Leishmania parasites that are transmitted through female sandfly bites. The disease is predominantly endemic to the tropics and...
Leishmaniasis is caused by protozoan Leishmania parasites that are transmitted through female sandfly bites. The disease is predominantly endemic to the tropics and semi-tropics and has been reported in more than 98 countries. Due to the side effects of anti-Leishmania drugs and the emergence of drug-resistant isolates, there is currently no encouraging prospect of introducing an effective therapy for the disease. Hence, it seems that the key to disease control management is the introduction of an effective vaccine, particularly against its cutaneous form. Advances in understanding underlying immune mechanisms are feasibale using a variety of candidate antigens, including attenuated live parasites, crude antigens, pure or recombinant Leishmania proteins, Leishmania genes encoding protective proteins, as well as immune system activators from the saliva of parasite vectors. However, there is still no vaccine against different types of human leishmaniasis. In this study, we review the works conducted or being performed in this field.
Topics: Humans; Leishmania; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Vaccination
PubMed: 34952558
DOI: 10.52547/ibj.26.1.35 -
Trends in Parasitology Apr 2022The control of diseases caused by protozoan parasites is one of the United Nations' Sustainable Development Goals. In recent years much research effort has gone into... (Review)
Review
The control of diseases caused by protozoan parasites is one of the United Nations' Sustainable Development Goals. In recent years much research effort has gone into developing a new generation of live attenuated vaccines (LAVs) against malaria, Chagas disease and leishmaniasis. However, there is a bottleneck related to their biosafety, production, and distribution that slows downs further development. The success of irradiated or genetically attenuated sporozoites against malaria, added to the first LAV against leishmaniasis to be evaluated in clinical trials, is indicative that the drawbacks of LAVs are gradually being overcome. However, whether persistence of LAVs is a prerequisite for sustained long-term immunity remains to be clarified, and the procedures necessary for clinical evaluation of vaccine candidates need to be standardized.
Topics: Animals; Antigens, Protozoan; Leishmaniasis; Malaria; Malaria Vaccines; Protozoan Vaccines; Sporozoites; Vaccines, Attenuated
PubMed: 34896016
DOI: 10.1016/j.pt.2021.11.004 -
ChemMedChem Aug 2017Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by... (Review)
Review
Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required. The majority of current therapeutic trypanosomatid targets are enzymes or cell-surface receptors. Among these, eukaryotic protein kinases are a major group of protein targets whose modulation may be beneficial for the treatment of neglected tropical protozoan diseases. This review summarizes the finding of new hit compounds for neglected tropical protozoan diseases, by repurposing known human kinase inhibitors on trypanosomatids. Kinase inhibitors are grouped by human kinase family and discussed according to the screening (target-based or phenotypic) reported for these compounds on trypanosomatids. This collection aims to provide insight into repurposed human kinase inhibitors and their importance in the development of new chemical entities with potential beneficial effects on the diseases caused by trypanosomatids.
Topics: Drug Repositioning; Humans; Neglected Diseases; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protozoan Infections; Protozoan Vaccines
PubMed: 28590590
DOI: 10.1002/cmdc.201700259 -
Journal of Biomedical Semantics Apr 2024Pathogenic parasites are responsible for multiple diseases, such as malaria and Chagas disease, in humans and livestock. Traditionally, pathogenic parasites have been...
BACKGROUND
Pathogenic parasites are responsible for multiple diseases, such as malaria and Chagas disease, in humans and livestock. Traditionally, pathogenic parasites have been largely an evasive topic for vaccine design, with most successful vaccines only emerging recently. To aid vaccine design, the VIOLIN vaccine knowledgebase has collected vaccines from all sources to serve as a comprehensive vaccine knowledgebase. VIOLIN utilizes the Vaccine Ontology (VO) to standardize the modeling of vaccine data. VO did not model complex life cycles as seen in parasites. With the inclusion of successful parasite vaccines, an update in parasite vaccine modeling was needed.
RESULTS
VIOLIN was expanded to include 258 parasite vaccines against 23 protozoan species, and 607 new parasite vaccine-related terms were added to VO since 2022. The updated VO design for parasite vaccines accounts for parasite life stages and for transmission-blocking vaccines. A total of 356 terms from the Ontology of Parasite Lifecycle (OPL) were imported to VO to help represent the effect of different parasite life stages. A new VO class term, 'transmission-blocking vaccine,' was added to represent vaccines able to block infectious transmission, and one new VO object property, 'blocks transmission of pathogen via vaccine,' was added to link vaccine and pathogen in which the vaccine blocks the transmission of the pathogen. Additionally, our Gene Set Enrichment Analysis (GSEA) of 140 parasite antigens used in the parasitic vaccines identified enriched features. For example, significant patterns, such as signal, plasma membrane, and entry into host, were found in the antigens of the vaccines against two parasite species: Plasmodium falciparum and Toxoplasma gondii. The analysis found 18 out of the 140 parasite antigens involved with the malaria disease process. Moreover, a majority (15 out of 54) of P. falciparum parasite antigens are localized in the cell membrane. T. gondii antigens, in contrast, have a majority (19/24) of their proteins related to signaling pathways. The antigen-enriched patterns align with the life cycle stage patterns identified in our ontological parasite vaccine modeling.
CONCLUSIONS
The updated VO modeling and GSEA analysis capture the influence of the complex parasite life cycles and their associated antigens on vaccine development.
Topics: Biological Ontologies; Animals; Parasites; Protozoan Vaccines; Humans; Vaccines; Models, Biological
PubMed: 38664818
DOI: 10.1186/s13326-024-00307-0 -
Fish & Shellfish Immunology Aug 2017Ichthyophthirius multifiliis, the causative agent of white spot disease (ichthyophthiriasis) is a major burden for fish farmers and aquarists globally. The parasite... (Review)
Review
Ichthyophthirius multifiliis, the causative agent of white spot disease (ichthyophthiriasis) is a major burden for fish farmers and aquarists globally. The parasite infects the skin and the gills of freshwater fish, which may acquire a protective adaptive immune response against this disease, making vaccine strategies feasible. However, there is no prophylactic treatment available and repetitive treatments with auxiliary substances are needed to control the infection. Historically, a variety of drugs and chemicals have been used to combat the disease but due to changing regulations and recognition of carcinogenic and environmentally damaging effects the most efficient compounds are prohibited. A continuous search for novel substances, which are highly effective against the parasites and harmless for the fish is ongoing. These compounds should be environmentally friendly and cost-effective. This review presents recent progress within host immunology, vaccinology and a description of novel substances, which have been tested as treatments against ichthyophthiriasis.
Topics: Animals; Ciliophora Infections; Fish Diseases; Fishes; Hymenostomatida; Protozoan Vaccines
PubMed: 28634009
DOI: 10.1016/j.fsi.2017.06.044 -
Vaccine Jun 2022Coccidiosis, caused by Eimeria protozoan species, is an economically important enteric disease of poultry. Although commercial live vaccines are widely used for disease...
Coccidiosis, caused by Eimeria protozoan species, is an economically important enteric disease of poultry. Although commercial live vaccines are widely used for disease control, the vaccine-induced protective immune mechanisms are poorly characterized. The present study used a commercial broiler vaccine containing a mixture of E. acervulina, E. maxima, and E. tenella. One-day-old chicks were vaccinated by spray followed by a challenge at 21 days of age with a mixture of wild type Eimeria species via oral gavage. Oocyst shedding, immune gene expression and cellular responses in the spleen and cecal tonsils were measured at pre- (days 14 and 21) and post-challenge (days 24, 28 and 35) time points. Results showed that the oocyst counts were significantly reduced in the vaccinated chickens at post-challenge compared to unvaccinated control group. While the vaccinated birds had a significantly increased toll-like receptor (TLR) 21 gene expression at pre-challenge, the transcription of interferon (IFN)γ, Interleukin (IL)-12 and CD40 genes in spleen and cecal tonsils of these birds was significantly higher at post-challenge compared to unvaccinated chickens. Cellular immunophenotyping analysis found that vaccination led to increased frequency of macrophages and activated T cells (CD8CD44 and CD4CD44) in the spleen and cecal tonsils at post-challenge. Furthermore, in vitro stimulation of chicken macrophages (MQ-NCSU cells) with purified individual species of E. acervulina, E. maxima, and E. tenella showed a significantly increased expression of TLR21, TLR2 and IFNγ genes as well as nitric oxide production. Collectively, these findings suggest that TLR21 and TLR2 may be involved in the immune cell recognition of Eimeria parasites and that the vaccine can induce a robust macrophage activation leading to a T helper-1 dominated protective response at both local and systemic lymphoid tissues.
Topics: Animals; Chickens; Coccidiosis; Eimeria; Eimeria tenella; Immunity; Oocysts; Poultry Diseases; Protozoan Vaccines; Toll-Like Receptor 2
PubMed: 35623907
DOI: 10.1016/j.vaccine.2022.05.043 -
Revista Da Sociedade Brasileira de... 2016Visceral leishmaniasis (VL) is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related... (Review)
Review
Visceral leishmaniasis (VL) is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related to the development of parasite resistance and side effects associated with the compounds used have been noted. Hence, alternative approaches for VL control are desirable. Some methods, such as vector control and culling of infected dogs, are insufficiently effective, with the latter not ethically recommended. The development of vaccines to prevent VL is a feasible and desirable measure for disease control; for example, some vaccines designed to protect dogs against VL have recently been brought to market. These vaccines are based on the combination of parasite fractions or recombinant proteins with adjuvants that are able to induce cellular immune responses; however, their partial efficacy and the absence of a vaccine to protect against human leishmaniasis underline the need for characterization of new vaccine candidates. This review presents recent advances in control measures for VL based on vaccine development, describing extensively studied antigens, as well as new antigenic proteins recently identified using immuno-proteomic techniques.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Dogs; Humans; Leishmania; Leishmaniasis, Visceral; Protozoan Proteins; Protozoan Vaccines
PubMed: 27598624
DOI: 10.1590/0037-8682-0120-2016 -
Molekuliarnaia Biologiia 2015Many innovative researches on the development and introduction of recombinant vaccines against many economically important parasites were carried out in the 20th... (Review)
Review
Many innovative researches on the development and introduction of recombinant vaccines against many economically important parasites were carried out in the 20th century. Research continues to hold promise with the development of immunological and molecular approaches for control of these parasites and in this regard it has already been seen that blood-sucking parasites such as Haemonchus contortus and Ostertagia ostertagi are susceptible to control by vaccines containing "novel" or "concealed" antigens. Haemonchus contortus is primarily pathogenic to sheep and its blood-feeding behaviour causes effects ranging from mild anaemia to mortality in young animals. Current means of control which are dependent on repeated treatment with anthelmintics are responsible for the increasing drug resistance of this parasite. Together with the growing concern of residual chemicals in the environment and food chain, this has led to attempts to better understand the biology of the parasite with an aim to develop alternate means of control, including the development of molecular vaccines. More problematic and also important is the formulation and delivery strategy to induce expulsion of this parasite, using vaccines containing recombinant "conventional" antigens. Tremendous progress has been made in the last decade in identifying several antigens from Haemonchus contortus which in their native form stimulate useful levels of protective immunity. Vaccines have been developed against H. contortus using 'novel' gut antigens from the parasite, but variable responsiveness of the host sheep has resulted in varying degrees of protection which are stimulated by these vaccines. Computer models have also been used to simulate vaccine efficacy in worm control and have yielded good results. This review will try to summarise the protective efficacy and also the molecular properties of principal candidate antigens which are expressed by this parasite. The review will try to cover the aspirations, current success, limitations and problems faced by researchers in the control of this economically important parasite.
Topics: Animals; Antigens, Helminth; Haemonchiasis; Haemonchus; Protozoan Vaccines; Sheep
PubMed: 26710767
DOI: 10.7868/S002689841506021X