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Zhongguo Xue Xi Chong Bing Fang Zhi Za... Feb 2018At present, there are no ideal drugs and measures in the treatment and prevention of toxoplasmosis. The development of safe, convenient, and strong protective nucleic... (Review)
Review
At present, there are no ideal drugs and measures in the treatment and prevention of toxoplasmosis. The development of safe, convenient, and strong protective nucleic acid vaccine is an important strategy for prevention and control of toxoplasmosis. The rhoptry protein (ROP) is a large class of proteins secreted by . ROPs play an important role in the invasion of host cells, the formation of parsitophorous vacuole (PV) and the regulation of proliferation by . Thus, ROPs become the most promising candidates of vaccine. In this paper, we summarize the important members of the ROPs, the expression vector and the immunogenicity and immunoprotection of the nucleic acid vaccine in animal experiments.
Topics: Animals; Antibodies, Protozoan; Protozoan Proteins; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccines, DNA
PubMed: 29536720
DOI: 10.16250/j.32.1374.2017162 -
EBioMedicine Mar 2019
Topics: Humans; Parasitic Diseases; Protozoan Vaccines; Venezuela
PubMed: 30929743
DOI: 10.1016/j.ebiom.2019.03.039 -
Frontiers in Cellular and Infection... 2020Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination... (Review)
Review
Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite vaccine candidates. Reflections on the development of an anti- vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different strains. Effective vaccines depend on our understanding of the (1) protective host immune response during invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.
Topics: Animals; Antibodies, Protozoan; Humans; Livestock; Mice; Parasites; Protozoan Proteins; Protozoan Vaccines; Toxoplasma; Toxoplasmosis, Animal
PubMed: 33324583
DOI: 10.3389/fcimb.2020.607198 -
Microbial Pathogenesis Sep 2021Toxoplasma gondii has a very wide host range and infects all warm-blooded animals including humans. The disease causes great economic losses both in animals and humans....
Toxoplasma gondii has a very wide host range and infects all warm-blooded animals including humans. The disease causes great economic losses both in animals and humans. Vaccination is the most effective approach to fight against toxoplasmosis however an effective vaccine has not been developed yet. In the present study, GRA8 protein of T. gondii that showed high immunogenicity in our previous microarray screening study was used to develop a DNA vaccine using pcDNA 3.3 vector for the first time. In order to increase the potency of the DNA vaccine, 10 times lower amount of GRA8 DNA vaccine was combined with molecular adjuvant CpG and formulated into a commercial liposome (pcDNA3.3-GRA8+CpG+Escort). Mice were vaccinated intramuscularly two times at three-week intervals and challenged orally with the T. gondii PRU strain tissue cysts. The humoral immune response was determined by Western Blot and ELISA. The cellular immune response was analyzed by flow cytometry, cytokine ELISA and MTT assay. Among the vaccine groups, pcDNA3.3-GRA8 and pcDNA3.3-GRA8+CpG+Escort induced strong IgG response compared to controls (P < 0.001). The IgG1 and IgG2a responses showed a balanced Th1-Th2 polarization. The ratio of CD4 and CD8 T lymphocytes secreting IFN-γ increased, and significantly higher extracellular IFN-γ secretion was achieved compared to the controls (P < 0.01). The amount of tissue cysts in the group of mice vaccinated with pcDNA3.3-GRA8 decreased significantly compared to control groups (P < 0.0001). In the group vaccinated with pcDNA3.3-GRA8+CpG+Escort, the amount of tissue cysts also decreased significantly compared to PBS (P = 0.0086) and Empty plasmid+CpG+Escort (P = 0.0007) groups. This study showed for the first time that pcDNA 3.3. vector encoding GRA8 with or without CpG and Liposome can induce strong cellular and humoral immune responses and confer strong protection against mouse model of chronic toxoplasmosis.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Mice; Mice, Inbred BALB C; Protozoan Proteins; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Animal; Vaccines, DNA
PubMed: 34098019
DOI: 10.1016/j.micpath.2021.105016 -
Frontiers in Immunology 2022Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally...
Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of , and their immunogenicity in cattle. p67C is a truncation of p67, the major surface protein of the sporozoite stage of , an apicomplexan parasite that causes an often-fatal bovine disease called East Coast fever (ECF) in sub-Saharan Africa. Compared to I32-19 and I32-28, we found that I53-50 nanoparticle scaffolds displaying p67C had the best biophysical characteristics. p67C-I53-50 also outperformed the other two nanoparticles in stimulating p67C-specific IgG1 and IgG2 antibodies and CD4 T-cell responses, as well as sporozoite neutralizing capacity. In experimental cattle vaccine trials, p67C-I53-50 induced significant immunity to ECF, suggesting that the I53-50 scaffold is a promising candidate for developing novel nanoparticle vaccines. To our knowledge this is the first application of computationally designed nanoparticles to the development of livestock vaccines.
Topics: Cattle; Animals; Theileriasis; Protozoan Vaccines; Cattle Diseases; Theileria parva; Antigens
PubMed: 36713406
DOI: 10.3389/fimmu.2022.1015840 -
The Korean Journal of Parasitology Aug 2014Babesia gibsoni is an intraerythrocytic apicomplexan parasite that causes piroplasmosis in dogs. B. gibsoni infection is characterized clinically by fever, regenerative... (Review)
Review
Babesia gibsoni is an intraerythrocytic apicomplexan parasite that causes piroplasmosis in dogs. B. gibsoni infection is characterized clinically by fever, regenerative anemia, splenomegaly, and sometimes death. Since no vaccine is available, rapid and accurate diagnosis and prompt treatment of infected animals are required to control this disease. Over the past decade, several candidate molecules have been identified using biomolecular techniques in the authors' laboratory for the development of a serodiagnostic method, vaccine, and drug for B. gibsoni. This review article describes newly identified candidate molecules and their applications for diagnosis, vaccine production, and drug development of B. gibsoni.
Topics: Animals; Antigens, Protozoan; Antiprotozoal Agents; Babesia; Babesiosis; Dogs; Drug Discovery; Protozoan Vaccines
PubMed: 25246713
DOI: 10.3347/kjp.2014.52.4.345 -
Parasites & Vectors Jul 2016Light is known to excite photosensitizers (PS) to produce cytotoxic reactive oxygen species (ROS) in the presence of oxygen. This modality is attractive for designing... (Review)
Review
Light is known to excite photosensitizers (PS) to produce cytotoxic reactive oxygen species (ROS) in the presence of oxygen. This modality is attractive for designing control measures against animal diseases and pests. Many PS have a proven safety record. Also, the ROS cytotoxicity selects no resistant mutants, unlike other drugs and pesticides. Photodynamic therapy (PDT) refers to the use of PS as light activable tumoricides, microbicides and pesticides in medicine and agriculture.Here we describe "photodynamic vaccination" (PDV) that uses PDT-inactivation of parasites, i.e. Leishmania as whole-cell vaccines against leishmaniasis, and as a universal carrier to deliver transgenic add-on vaccines against other infectious and malignant diseases. The efficacy of Leishmania for vaccine delivery makes use of their inherent attributes to parasitize antigen (vaccine)-presenting cells. Inactivation of Leishmania by PDT provides safety for their use. This is accomplished in two different ways: (i) chemical engineering of PS to enhance their uptake, e.g. Si-phthalocyanines; and (ii) transgenic approach to render Leishmania inducible for porphyrinogenesis. Three different schemes of Leishmania-based PDV are presented diagrammatically to depict the cellular events resulting in cell-mediated immunity, as seen experimentally against leishmaniasis and Leishmania-delivered antigen in vitro and in vivo. Safety versus efficacy evaluations are under way for PDT-inactivated Leishmania, including those further processed to facilitate their storage and transport. Leishmania transfected to express cancer and viral vaccine candidates are being prepared accordingly for experimental trials.We have begun to examine PS-mediated photodynamic insecticides (PDI). Mosquito cells take up rose bengal/cyanosine, rendering them light-sensitive to undergo disintegration in vitro, thereby providing a cellular basis for the larvicidal activity seen by the same treatments. Ineffectiveness of phthalocyanines and porphyrins for PDI underscores its requirement for different PS. Differential uptake of PS by insect versus other cells to account for this difference is under study.The ongoing work is patterned after the one-world approach by enlisting the participation of experts in medicinal chemistry, cell/molecular biology, immunology, parasitology, entomology, cancer research, tropical medicine and veterinary medicine. The availability of multidisciplinary expertise is indispensable for implementation of the necessary studies to move the project toward product development.
Topics: Animals; Cell Survival; Drug Carriers; Insecticides; Leishmania; Mosquito Control; Photosensitizing Agents; Protozoan Vaccines; Vaccination
PubMed: 27412129
DOI: 10.1186/s13071-016-1674-3 -
Acta Tropica Dec 2019Leishmanization (LZ) is an intradermal inoculation of live Leishmania to induce an artificial cutaneous leishmaniasis (CL) lesion in a covered part of the body to... (Review)
Review
Leishmanization (LZ) is an intradermal inoculation of live Leishmania to induce an artificial cutaneous leishmaniasis (CL) lesion in a covered part of the body to protect against further natural CL lesion development. Leishmanization has been used from ancient times and when NNN medium was developed continued with using Leishmania from culture media. The objective of this study was to review LZ published experiences. This article is a review of LZ experiences and historical studies initiated since 1910 when Leishmania promastigotes were harvested from culture media and used for LZ. This review includes LZ experiences in Israel, some countries of Former Soviet Union and Iran. The results of LZ in Israel, some countries of Former Soviet Union and Iran showed that despite limitations, using this method significantly reduced the incidence rate of CL among leishmanized individuals in endemic areas. In conclusion, leishmanization using Leishmania major produced under GMP guideline is a valuable tool to protect against CL, there are limitations which need further study.
Topics: Humans; Leishmania major; Leishmaniasis, Cutaneous; Protozoan Vaccines; Vaccination
PubMed: 31525323
DOI: 10.1016/j.actatropica.2019.105173 -
Nature Jul 2021Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important...
Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock. An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms-including antigenic variation-that present an apparently insurmountable barrier to vaccination. Here we show, using a systematic genome-led vaccinology approach and a mouse model of Trypanosoma vivax infection, that protective invariant subunit vaccine antigens can be identified. Vaccination with a single recombinant protein comprising the extracellular region of a conserved cell-surface protein that is localized to the flagellum membrane (which we term 'invariant flagellum antigen from T. vivax') induced long-lasting protection. Immunity was passively transferred with immune serum, and recombinant monoclonal antibodies to this protein could induce sterile protection and revealed several mechanisms of antibody-mediated immunity, including a major role for complement. Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained socioeconomic development in countries in sub-Saharan Africa, and provides evidence that highly protective vaccines against trypanosome infections can be achieved.
Topics: Animals; Antigens, Protozoan; Complement System Proteins; Conserved Sequence; Disease Models, Animal; Female; Flagella; Mice; Mice, Inbred BALB C; Protozoan Vaccines; Time Factors; Trypanosoma vivax; Trypanosomiasis, African; Vaccines, Subunit
PubMed: 34040257
DOI: 10.1038/s41586-021-03597-x -
Trends in Parasitology Jun 2019The generation of an efficacious vaccine that elicits protective CD4 T cell-mediated immunity has been elusive. The lack of a vaccine against the Leishmania parasite is... (Review)
Review
The generation of an efficacious vaccine that elicits protective CD4 T cell-mediated immunity has been elusive. The lack of a vaccine against the Leishmania parasite is particularly perplexing as infected individuals acquire life-long immunity to reinfection. Experimental observations suggest that the relationship between immunological memory and protection against Leishmania is not straightforward and that a new paradigm is required to inform vaccine design. These observations include: (i) induction of Th1 memory is a component of protective immunity, but is not sufficient; (ii) memory T cells may be protective only if they generate circulating effector cells prior to, not after, challenge; and (iii) the low-dose/high-inflammation conditions of physiological vector transmission compromises vaccine efficacy. Understanding the implications of these observations is likely key to efficacious vaccination.
Topics: Animals; Antigens, Protozoan; CD4-Positive T-Lymphocytes; Humans; Immunity, Cellular; Leishmania; Protozoan Vaccines; Vaccination
PubMed: 31080088
DOI: 10.1016/j.pt.2019.04.002