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Drug Design, Development and Therapy 2018Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this... (Review)
Review
Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results.
Topics: Animals; Antigens, Protozoan; Drug Resistance; Drug Therapy, Combination; Humans; Leishmania; Leishmaniasis; Leishmaniasis Vaccines; Treatment Outcome; Trypanocidal Agents
PubMed: 29317800
DOI: 10.2147/DDDT.S146521 -
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 -
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 -
Frontiers in Immunology 2021Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of... (Review)
Review
Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.
Topics: Animals; Coinfection; Drug Design; Drug Development; Endemic Diseases; Host-Parasite Interactions; Humans; Immunogenicity, Vaccine; Praziquantel; Protozoan Vaccines; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 33746974
DOI: 10.3389/fimmu.2021.635985 -
Parasites & Vectors Jul 2015Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. It has extensive host populations and is prevalent globally; T. gondii infection can cause... (Review)
Review
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. It has extensive host populations and is prevalent globally; T. gondii infection can cause a zoonotic parasitic disease. Microneme protein 3 (MIC3) is a secreted protein that is expressed in all stages of the T. gondii life cycle. It has strong immunoreactivity and plays an important role in the recognition, adhesion and invasion of host cells by T. gondii. This article reviews the molecular structure of MIC3, its role in the invasion of host cells by parasites, its relationship with parasite virulence, and its induction of immune protection to lay a solid foundation for an in-depth study of potential diagnostic agents and vaccines for preventing toxoplasmosis.
Topics: Amino Acid Sequence; Animals; Cell Adhesion; Humans; Life Cycle Stages; Molecular Sequence Data; Protozoan Proteins; Protozoan Vaccines; Sequence Alignment; Toxoplasma; Toxoplasmosis, Animal; Vaccines, DNA; Virulence
PubMed: 26194005
DOI: 10.1186/s13071-015-1001-4 -
Expert Review of Vaccines Feb 2021causes significant public health problems in endemic regions. A vaccine to prevent disease is critical, considering the rapid spread of drug-resistant parasite strains,... (Review)
Review
INTRODUCTION
causes significant public health problems in endemic regions. A vaccine to prevent disease is critical, considering the rapid spread of drug-resistant parasite strains, and the development of hypnozoites in the liver with potential for relapse. A minimally effective vaccine should prevent disease and transmission while an ideal vaccine provides sterile immunity.
AREAS COVERED
Despite decades of research, the complex life cycle, technical challenges and a lack of funding have hampered progress of vaccine development. Here, we review the progress of potential vaccine candidates from different stages of the parasite life cycle. We also highlight the challenges and important strategies for rational vaccine design. These factors can significantly increase immune effector mechanisms and improve the protective efficacy of these candidates in clinical trials to generate sustained protection over longer periods of time.
EXPERT OPINION
A vaccine that presents functionally-conserved epitopes from multiple antigens from various stages of the parasite life cycle is key to induce broadly neutralizing strain-transcending protective immunity to effectively disrupt parasite development and transmission.
Topics: Animals; Antigens, Protozoan; Drug Resistance; Humans; Liver; Malaria Vaccines; Malaria, Vivax; Plasmodium vivax; Recurrence; Time Factors
PubMed: 33481638
DOI: 10.1080/14760584.2021.1880898 -
Frontiers in Cellular and Infection... 2019
Topics: Antiprotozoal Agents; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Protozoan Infections; Protozoan Vaccines; Trypanosoma; Trypanosomiasis
PubMed: 31448246
DOI: 10.3389/fcimb.2019.00293 -
Frontiers in Immunology 2021In areas where transmission is endemic, clinical immunity against malaria is progressively acquired during childhood and adults are usually protected against the severe... (Review)
Review
In areas where transmission is endemic, clinical immunity against malaria is progressively acquired during childhood and adults are usually protected against the severe clinical consequences of the disease. Nevertheless, pregnant women, notably during their first pregnancies, are susceptible to placental malaria and the associated serious clinical outcomes. Placental malaria is characterized by the massive accumulation of infected erythrocytes and monocytes in the placental intervillous spaces leading to maternal anaemia, hypertension, stillbirth and low birth weight due to premature delivery, and foetal growth retardation. Remarkably, the prevalence of placental malaria sharply decreases with successive pregnancies. This protection is associated with the development of antibodies directed towards the surface of -infected erythrocytes from placental origin. Placental sequestration is mediated by the interaction between VAR2CSA, a member of the erythrocyte membrane protein 1 family expressed on the infected erythrocytes surface, and the placental receptor chondroitin sulfate A. VAR2CSA stands today as the leading candidate for a placental malaria vaccine. We recently reported the safety and immunogenicity of two VAR2CSA-derived placental malaria vaccines (PRIMVAC and PAMVAC), spanning the chondroitin sulfate A-binding region of VAR2CSA, in both malaria-naïve and -exposed non-pregnant women in two distinct Phase I clinical trials (ClinicalTrials.gov, NCT02658253 and NCT02647489). This review discusses recent advances in placental malaria vaccine development, with a focus on the recent clinical data, and discusses the next clinical steps to undertake in order to better comprehend vaccine-induced immunity and accelerate vaccine development.
Topics: Animals; Antigens, Protozoan; Drug Development; Female; Host-Parasite Interactions; Humans; Immunization; Immunogenicity, Vaccine; Malaria Vaccines; Malaria, Falciparum; Placenta; Pregnancy; Pregnancy Complications, Parasitic; Treatment Outcome
PubMed: 33717176
DOI: 10.3389/fimmu.2021.634508 -
Infection, Genetics and Evolution :... Nov 2017Eimeria species parasites can cause the disease coccidiosis, most notably in chickens. The occurrence of coccidiosis is currently controlled through a combination of... (Review)
Review
Eimeria species parasites can cause the disease coccidiosis, most notably in chickens. The occurrence of coccidiosis is currently controlled through a combination of good husbandry, chemoprophylaxis and/or live parasite vaccination; however, scalable, cost-effective subunit or recombinant vaccines are required. Many antigens have been proposed for use in novel anticoccidial vaccines, supported by the capacity to reduce disease severity or parasite replication, increase body weight gain in the face of challenge or improve feed conversion under experimental conditions, but none has reached commercial development. Nonetheless, the protection against challenge induced by some antigens has been within the lower range described for the ionophores against susceptible isolates or current live vaccines prior to oocyst recycling. With such levels of efficacy it may be that combinations of anticoccidial antigens already described are sufficient for development as novel multi-valent vaccines, pending identification of optimal delivery systems. Selection of the best antigens to be included in such vaccines can be informed by knowledge defining the natural occurrence of specific antigenic diversity, with relevance to the risk of immediate vaccine breakthrough, and the rate at which parasite genomes can evolve new diversity. For Eimeria, such data are now becoming available for antigens such as apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1) and more are anticipated as high-capacity, high-throughput sequencing technologies become increasingly accessible.
Topics: Animals; Antigenic Variation; Chickens; Coccidia; Coccidiosis; Coccidiostats; Protozoan Vaccines; Vaccines, Synthetic
PubMed: 29017798
DOI: 10.1016/j.meegid.2017.10.009