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Advances in Parasitology 2019Infection with Giardia produces a wide range of clinical outcomes. Acutely infected patients may have no overt symptoms or suffer from severe cramps, diarrhea, nausea... (Review)
Review
Infection with Giardia produces a wide range of clinical outcomes. Acutely infected patients may have no overt symptoms or suffer from severe cramps, diarrhea, nausea and even urticaria. Recently, post-infectious irritable bowel syndrome and chronic fatigue syndrome have been identified as long-term sequelae of giardiasis. Frequently, recurrent and chronic Giardia infection is considered a major contributor to stunting in children from low and middle income countries. Perhaps the most unusual outcome of infection with Giardia is the apparent reduced risk of developing moderate-to-severe diarrhea due to other enteric infections which has been noted in several recent studies. The goal of understanding immune responses against Giardia is therefore to identify protective mechanisms which could become targets for vaccine development, but also to identify mechanisms whereby infections lead to these other diverse outcomes. Giardia induces a robust adaptive immune response in both humans and animals. It has been known for many years that there is production of large amounts of parasite-specific IgA following infection and that CD4 T cell responses contribute to this IgA production and control of the infection. In the past decade, there have been advances in our understanding of the non-antibody effector mechanisms used by the host to fight Giardia infections, in particular the importance of the cytokine interleukin (IL)-17 in orchestrating these responses. There have also been major advances in understanding how the innate response to Giardia infection is initiated and how it contributes to the development of adaptive immunity. Finally, there here have been significant increases in our knowledge of how the resident microbial community influences the immune response and how these responses contribute to the development of some of the symptoms of giardiasis. In this article, we will focus on data generated in the last 10 years and how it has advanced our knowledge about this important parasitic disease.
Topics: Adaptive Immunity; Animals; Giardia; Giardiasis; Humans; Immunity, Innate; Protozoan Vaccines
PubMed: 31630758
DOI: 10.1016/bs.apar.2019.07.004 -
PLoS Neglected Tropical Diseases May 2021The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet,... (Review)
Review
The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.
Topics: Animals; Anthelmintics; Antibodies, Helminth; B-Lymphocytes; Germinal Center; Helminthiasis; Helminths; Humans; Intestinal Diseases, Parasitic; Mice; Protozoan Vaccines; Reinfection; T-Lymphocytes, Helper-Inducer
PubMed: 33983946
DOI: 10.1371/journal.pntd.0009340 -
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 -
Poultry Science Oct 2023Coccidiosis is a parasitic disease in the intestine caused by the genus Eimeria that poses a substantial economic threat to the broiler breeding industry. The misuse of...
Coccidiosis is a parasitic disease in the intestine caused by the genus Eimeria that poses a substantial economic threat to the broiler breeding industry. The misuse of chemoprophylaxis and live oocyst vaccines has a negative impact on chicken reproductivity. Therefore, there is a pressing need to develop safe, convenient, and effective vaccines. Lactic acid bacteria can be used as a means to deliver mucosal vaccines against intestinal pathogens, which is a promising strategy. In this study, a recombinant Lactobacillus plantarum (L. plantarum) with surface-expressed antigens constructed from the fusion of Eimeria tenella (E. tenella) antigen profilin and the Salmonella enterica serovar Typhimurium flagellin protein FliC was created. After oral immunization with the recombinant L. plantarum, T-cell differentiation was analyzed by flow cytometry, and specific antibody levels were determined via indirect ELISA. Oocyst shedding, body weight, and cecum lesions were assessed as measures of protective immunity after challenge with E. tenella. The results of this study demonstrate the effectiveness of recombinant L. plantarum as an immunization agent for chickens. Specific IgA titers in the intestine and specific IgG antibody titers in the serum were significantly higher in chickens immunized with recombinant L. plantarum (P < 0.001). Additionally, the levels of IL-2 (P < 0.05) and IFN-γ (P < 0.01) in the serum were markedly increased. Recombinant L. plantarum induced T-cell differentiation, resulting in a higher proportion of CD4 and CD8 T cells in splenocytes (P < 0.001). Fecal oocyst shedding in the immunized group was significantly reduced (P < 0.001). Additionally, recombinant L. plantarum significantly relieved pathological damage in the cecum, as evidenced by lesion scores (P < 0.01) and histopathological cecum sections. In conclusion, the present study provides evidence to support the possibility of using L. plantarum as a promising carrier for the delivery of protective antigens to effectively protect chickens against coccidiosis.
Topics: Animals; Chickens; Eimeria tenella; Profilins; Lactobacillus plantarum; Flagellin; CD8-Positive T-Lymphocytes; Antigens, Surface; Coccidiosis; Protozoan Vaccines; Poultry Diseases
PubMed: 37516003
DOI: 10.1016/j.psj.2023.102945 -
BMC Medicine Sep 2021
Topics: Antibodies, Protozoan; Antigens, Protozoan; Erythrocytes; Female; Humans; Malaria Vaccines; Malaria, Falciparum; Placenta; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic
PubMed: 34503499
DOI: 10.1186/s12916-021-02083-5 -
Revista Do Instituto de Medicina... 2022Despite the many efforts of researchers around the world, there is currently no effective vaccine for malaria. Numerous studies have been developed to find vaccine... (Review)
Review
Despite the many efforts of researchers around the world, there is currently no effective vaccine for malaria. Numerous studies have been developed to find vaccine antigens that are immunogenic and safe. Among antigen candidates, Plasmodium falciparum merozoite surface protein 3 (MSP3) has stood out in a number of these studies for its ability to induce a consistent and protective immune response, also being safe for use in humans. This review presents the main studies that explored MSP3 as a vaccine candidate over the last few decades. MSP3 formulations were tested in animals and humans and the most advanced candidate formulations are MSP3-LSP, a combination of MSP3 and LSP1, and GMZ2 (a vaccine based on the recombinant protein fusion GLURP and MSP3) which is currently being tested in phase II clinical studies. This brief review highlights the history and the main formulations of MSP3-based vaccines approaches against P. falciparum .
Topics: Animals; Antibodies, Protozoan; Malaria Vaccines; Membrane Proteins; Merozoites; Plasmodium falciparum
PubMed: 35293561
DOI: 10.1590/S1678-9946202264023 -
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 -
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 -
Parasitology Mar 2016Neospora caninum is a leading cause of abortion in cattle, and is thus an important veterinary health problem of high economic significance. Vaccination has been... (Review)
Review
Neospora caninum is a leading cause of abortion in cattle, and is thus an important veterinary health problem of high economic significance. Vaccination has been considered a viable strategy to prevent bovine neosporosis. Different approaches have been investigated, and to date the most promising results have been achieved with live-attenuated vaccines. Subunit vaccines have also been studied, and most of them represented components that are functionally involved in (i) the physical interaction between the parasite and its host cell during invasion or (ii) tachyzoite-to-bradyzoite stage conversion. Drugs have been considered as an option to limit the effects of vertical transmission of N. caninum. Promising results with a small panel of compounds in small laboratory animal models indicate the potential value of a chemotherapeutical approach for the prevention of neosporosis in ruminants. For both, vaccines and drugs, the key for success in preventing vertical transmission lies in the application of bioactive compounds that limit parasite proliferation and dissemination, without endangering the developing fetus not only during an exogenous acute infection but also during recrudescence of a chronic infection. In this review, the current status of vaccine and drug development is presented and novel strategies against neosporosis are discussed.
Topics: Animals; Cattle; Cattle Diseases; Coccidiosis; Disease Models, Animal; Infectious Disease Transmission, Vertical; Mice; Neospora; Protozoan Vaccines; Sheep; Sheep Diseases; Vaccination
PubMed: 26626124
DOI: 10.1017/S0031182015001596