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Vaccine Jul 2019Since the discovery of Toxoplasma gondii in 1908, it is estimated that one-third of the global population has been exposed to this ubiquitous intracellular protozoan.... (Review)
Review
Since the discovery of Toxoplasma gondii in 1908, it is estimated that one-third of the global population has been exposed to this ubiquitous intracellular protozoan. The complex life cycle of T. gondii has enabled itself to overcome stress and transmit easily within a broad host range thus achieving a high seroprevalence worldwide. To date, toxoplasmosis remains one of the most prevalent HIV-associated opportunistic central nervous system infections. This review presents a comprehensive overview of different vaccination approaches ranging from traditional inactivated whole-T. gondii vaccines to the popular DNA vaccines. Extensive discussions are made to highlight the challenges in constructing these vaccines, selecting adjuvants as well as delivery methods, immunisation approaches and developing study models. Herein we also deliberate over the latest and promising enhancement strategies that can address the limitations in developing an effective T. gondii prophylactic vaccine.
Topics: Animals; Humans; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccination; Vaccines, DNA
PubMed: 31186188
DOI: 10.1016/j.vaccine.2019.05.083 -
Parasite Immunology Dec 2016Bovine neosporosis is a worldwide concern due to its global distribution and great economic impact. Reproductive failure in cattle due to abortion leads to major... (Review)
Review
Bovine neosporosis is a worldwide concern due to its global distribution and great economic impact. Reproductive failure in cattle due to abortion leads to major economic losses associated with the disease. Currently, there is no treatment or vaccine available against abortion or transmission caused by Neospora caninum infection in cattle. However, vaccination is considered the best measure of control against bovine neosporosis. Several host and parasite factors can influence the dynamics of the infection in bovines. Moreover, the availability of well-defined infection models is a key factor for the evaluation of vaccine candidates. However, working with cattle is not easy due to difficult handling, facilities and costs, and therefore, 'more affordable' models could be used for screening of promising vaccines to establish proof of concept. So far, live-attenuated vaccines have shown good efficacy against exogenous transplacental transmission; however, they have relevant disadvantages and associated risks, which render inactivated or subunit vaccines the best way forward. The identification of novel potential targets and vaccines, and the application of innovative vaccine technologies in harmonized experimental animal models, will accelerate the development of an effective vaccine against bovine neosporosis.
Topics: Animals; Cattle; Cattle Diseases; Coccidiosis; Disease Models, Animal; Neospora; Protozoan Vaccines; Vaccination; Vaccines, Attenuated
PubMed: 27314818
DOI: 10.1111/pim.12342 -
Drug Resistance Updates : Reviews and... May 2019Entamoeba histolytica is the etiological agent of amebiasis, which is an endemic parasitic disease in developing countries and is the cause of approximately 70,000... (Review)
Review
Entamoeba histolytica is the etiological agent of amebiasis, which is an endemic parasitic disease in developing countries and is the cause of approximately 70,000 deaths annually. E. histolytica trophozoites usually reside in the colon as a non-pathogenic commensal in most infected individuals (90% of infected individuals are asymptomatic). For unknown reasons, these trophozoites can become virulent and invasive, cause amebic dysentery, and migrate to the liver where they cause hepatocellular damage. Amebiasis is usually treated either by amebicides which are classified as (a) luminal and are active against the luminal forms of the parasite, (b) tissue and are effective against those parasites that have invaded tissues, and (c) mixed and are effective against the luminal forms of the parasite and those forms which invaded the host's tissues. Of the amebicides, the luminal amebicide, metronidazole (MTZ), is the most widely used drug to treat amebiasis. Although well tolerated, concerns about its adverse effects and the possible emergence of MTZ-resistant strains of E. histolytica have led to the development of new therapeutic strategies against amebiasis. These strategies include improving the potency of existing amebicides, discovering new uses for approved drugs (repurposing of existing drugs), drug rediscovery, vaccination, drug targeting of essential E. histolytica components, and the use of probiotics and bioactive natural products. This review examines each of these strategies in the light of the current knowledge on the gut microbiota of patients with amebiasis.
Topics: Amebiasis; Amebicides; Animals; Biological Products; Colon; Drug Repositioning; Entamoeba histolytica; Gastrointestinal Microbiome; Host-Parasite Interactions; Humans; Liver; Metronidazole; Microbial Interactions; Molecular Targeted Therapy; Probiotics; Protozoan Vaccines; Severity of Illness Index
PubMed: 31112766
DOI: 10.1016/j.drup.2019.04.003 -
Experimental Parasitology Mar 2020Cutaneous Leishmaniasis is a serious public health problem, typically affecting poor populations with limited access to health care. Control is largely dependent on... (Review)
Review
Cutaneous Leishmaniasis is a serious public health problem, typically affecting poor populations with limited access to health care. Control is largely dependent on chemotherapies that are inefficient, costly and challenging to deliver. Vaccination is an attractive and feasible alternative because long-term protection is typical in patients who recover from the disease. No human vaccine is yet approved for use, but several candidates are at various stages of testing. Live attenuated parasites, which stimulate long-term immune protection, have potential as effective vaccines, and their challenges relating to safety, formulation and delivery can be overcome. Here we review current data on the potential of live attenuated Leishmania vaccines and discuss possible routes to regulatory approval.
Topics: Animals; Disease Models, Animal; Humans; Leishmania; Leishmaniasis, Cutaneous; Protozoan Vaccines; Vaccines, Attenuated
PubMed: 32027892
DOI: 10.1016/j.exppara.2020.107849 -
Frontiers in Cellular and Infection... 2018Eukaryotic parasites and pathogens continue to cause some of the most detrimental and difficult to treat diseases (or disease states) in both humans and animals, while... (Review)
Review
Eukaryotic parasites and pathogens continue to cause some of the most detrimental and difficult to treat diseases (or disease states) in both humans and animals, while also continuously expanding into non-endemic countries. Combined with the ever growing number of reports on drug-resistance and the lack of effective treatment programs for many metazoan diseases, the impact that these organisms will have on quality of life remain a global challenge. Vaccination as an effective prophylactic treatment has been demonstrated for well over 200 years for bacterial and viral diseases. From the earliest variolation procedures to the cutting edge technologies employed today, many protective preparations have been successfully developed for use in both medical and veterinary applications. In spite of the successes of these applications in the discovery of subunit vaccines against prokaryotic pathogens, not many targets have been successfully developed into vaccines directed against metazoan parasites. With the current increase in -omics technologies and metadata for eukaryotic parasites, target discovery for vaccine development can be expedited. However, a good understanding of the host/vector/pathogen interface is needed to understand the underlying biological, biochemical and immunological components that will confer a protective response in the host animal. Therefore, systems biology is rapidly coming of age in the pursuit of effective parasite vaccines. Despite the difficulties, a number of approaches have been developed and applied to parasitic helminths and arthropods. This review will focus on key aspects of vaccine development that require attention in the battle against these metazoan parasites, as well as successes in the field of vaccine development for helminthiases and ectoparasites. Lastly, we propose future direction of applying successes in pursuit of next generation vaccines.
Topics: Animals; Antigens, Protozoan; Arthropods; Drug Discovery; Drug Resistance; Helminths; Host-Parasite Interactions; Metadata; Parasites; Parasitic Diseases, Animal; Protozoan Vaccines; Systems Biology; Vaccination
PubMed: 29594064
DOI: 10.3389/fcimb.2018.00067 -
Parasite Immunology Dec 2016African trypanosomes cause human and animal African trypanosomiases, which are chronic, debilitating and often fatal diseases of people and livestock in sub-Saharan... (Review)
Review
African trypanosomes cause human and animal African trypanosomiases, which are chronic, debilitating and often fatal diseases of people and livestock in sub-Saharan Africa. The extracellular protozoan parasites are exemplars of antigenic variation. They direct host-protective B-cell and T-cell immune responses towards hypervariable components of their variable surface glycoprotein coat and evade immune elimination by generating new surface coat antigenic variants at a rate that supersedes immune destruction. This results in recurring waves of parasitemia, tissue invasion and escalating immunopathology in trypanosomiasis-susceptible hosts. Here, we discuss the possibility that host control of African trypanosomes might be improved by immunization with conserved VSG peptides and invariant surface glycoproteins. Infection-induced T-cell recall responses to these typically poorly expressed or nonimmunogenic parasite components induce tissue phagocytes to produce microbicidal materials that kill trypanosomes. Preliminary data that support this immune-enhancing vaccine strategy are discussed, as are host and parasite interactions that might downregulate the protective responses. These include infection-induced immunosuppression and increasing virulence of infecting parasites over time.
Topics: Africa South of the Sahara; Animals; Antigenic Variation; B-Lymphocytes; Humans; Immunity, Innate; Parasitemia; Protozoan Vaccines; T-Lymphocytes; Trypanosoma; Trypanosomiasis, African; Vaccination
PubMed: 27636100
DOI: 10.1111/pim.12387 -
Comparative Immunology, Microbiology... Aug 2018Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a wide variety of vertebrates as intermediate hosts. The aim of the current systematic... (Review)
Review
Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a wide variety of vertebrates as intermediate hosts. The aim of the current systematic review study is to clarify the latest status of studies in the literature regarding rhoptry-associated recombinant proteins or rhoptry-associated recombinant DNAs as potential vaccines against toxoplasmosis. The search was performed systematically in 8 databases, four in English and four in Persian, up to February 2017. Overall, ROP2 was the most commonly used ROPs in DNA vaccines (27.27%) and protein vaccines (6.81%). Furthermore, regarding the type of adjuvants, route and dose of vaccination, animal models, challenge methods, and measurement of immune responses has been discussed in the text. It is hoped that this article help researchers to conduct more effective studies in the field of immunization against T. gondii.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Humans; Immunization; Protozoan Proteins; Protozoan Vaccines; Recombinant Proteins; Toxoplasma; Toxoplasmosis, Animal; Vaccination; Vaccines, DNA
PubMed: 30290885
DOI: 10.1016/j.cimid.2018.09.005 -
Trends in Parasitology Aug 2019The incidence and prevalence of babesiosis in animals and humans is increasing, yet prevention, control, or treatment measures remain limited and ineffective. Despite a... (Review)
Review
The incidence and prevalence of babesiosis in animals and humans is increasing, yet prevention, control, or treatment measures remain limited and ineffective. Despite a growing body of new knowledge of the biology, pathogenicity, and virulence of Babesia parasites, there is still no well-defined, adequately effective and easily deployable vaccine. While numerous published studies suggest that the development of such anti-Babesia vaccines should be feasible, many others identify significant challenges that need to be overcome in order to succeed. Here, we review historic and recent attempts in babesiosis vaccine discovery to avoid past pitfalls, learn new lessons, and provide a roadmap to guide the development of next-generation babesiosis vaccines.
Topics: Animals; Babesia; Babesiosis; History, 20th Century; History, 21st Century; Humans; Protozoan Vaccines
PubMed: 31281025
DOI: 10.1016/j.pt.2019.06.002 -
Frontiers in Immunology 2018Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to... (Review)
Review
Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to establish chronic infections is the targeting of pattern recognition receptors (PRRs) including toll-like receptors, C-type lectin receptors, and the inflammasome. Given the critical role of these receptors and their intracellular pathways in regulating innate inflammatory responses, and also directing adaptive immunity toward Th1 and Th2 responses, recognition of the pathways triggered and/or modulated by helminths and their products will provide detailed insights about how helminths are able to establish an immunoregulatory environment. However, helminths also target PRRs-independent mechanisms (and most likely other yet unknown mechanisms and pathways) underpinning the battery of different molecules helminths produce. Herein, the current knowledge on intracellular pathways in antigen presenting cells activated by helminth-derived biomolecules is reviewed. Furthermore, we discuss the importance of helminth-derived vesicles as a less-appreciated components released during infection, their role in activating these host intracellular pathways, and their implication in the development of new therapeutic approaches for inflammatory diseases and the possibility of designing a new generation of vaccines.
Topics: Animals; Biomarkers; Extracellular Vesicles; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Immune System; Immunomodulation; Intracellular Space; Protozoan Vaccines; Receptors, Pattern Recognition; Secretory Vesicles; Signal Transduction
PubMed: 30369927
DOI: 10.3389/fimmu.2018.02349 -
Expert Review of Vaccines 2023is a widespread protozoan with significant economic losses and public health importance. But so far, the protective effect of reported DNA-based vaccines fluctuates... (Review)
Review
INTRODUCTION
is a widespread protozoan with significant economic losses and public health importance. But so far, the protective effect of reported DNA-based vaccines fluctuates widely, and no study has demonstrated complete protection.
AREAS COVERED
This review provides an inclusive summary of DNA vaccine antigens, adjuvants, and some other parameters. A total of 140 articles from 2000 to 2021 were collected from five databases. By contrasting the outcomes of acute and chronic challenges, we aimed to investigate and identify viable immunological strategies for optimum protection. Furthermore, we evaluated and discussed the impact of several parameters on challenge outcomes in the hopes of developing some recommendations to assist better future horizontal comparisons among research.
EXPERT OPINION
In the coming five years of research, the exploration of vaccine cocktails combining invasion antigens and metabolic antigens with genetic adjuvants or novel DNA delivery methods may offer us desirable protection against this multiple stage of life parasite. In addition to finding a better immune strategy, developing better in silico prediction methods, solving problems posed by variables in practical applications, and gaining a more profound knowledge of -host molecular interaction is also crucial towards a successful vaccine.
Topics: Humans; Animals; Mice; Toxoplasma; Vaccines, DNA; Antigens, Protozoan; Protozoan Proteins; Protozoan Vaccines; Adjuvants, Immunologic; DNA; Antibodies, Protozoan; Mice, Inbred BALB C
PubMed: 36508550
DOI: 10.1080/14760584.2023.2157818