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The Journal of Parasitology Nov 2021Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of... (Review)
Review
Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of foodborne illness-related death. Currently, there exists no approved vaccine for humans or most livestock against the parasite. DNA vaccines, a type of subunit vaccine which uses segments of the pathogen's DNA to generate immunity, have shown varying degrees of experimental efficacy against infection caused by the parasite. This review compiles DNA vaccine efforts against Toxoplasma gondii, segmenting the analysis by parasite antigen, as well as a review of concomitant adjuvant usage. No single antigenic group was consistently more effective within in vivo trials relative to others.
Topics: Adjuvants, Immunologic; Animals; Antigens, Protozoan; Humans; Microneme; Protozoan Vaccines; Toxoplasma; Toxoplasmosis; Vaccines, DNA
PubMed: 34852176
DOI: 10.1645/20-157 -
Frontiers in Immunology 2021Schistosomiasis is a parasitic disease endemic to freshwater areas of Southeast Asia, Africa, and South America that is capable of causing serious damage to the internal... (Review)
Review
Schistosomiasis is a parasitic disease endemic to freshwater areas of Southeast Asia, Africa, and South America that is capable of causing serious damage to the internal organs. Recent studies have linked exosomes to the progression of schistosomiasis. These structures are important mediators for intercellular communication, assist cells to exchange proteins, lipids, and genetic material and have been shown to play critical roles during host-parasite interactions. This review aims to discuss the pathophysiology of exosomes in schistosomiasis and their roles in regulating the host immune response. Understanding how exosomes are involved in the pathogenesis of schistosomiasis may provide new perspectives in diagnosing and treating this neglected disease.
Topics: Animals; Exosomes; Host-Pathogen Interactions; Humans; Prognosis; Protozoan Vaccines; Schistosoma; Schistosomiasis; Schistosomicides; Signal Transduction
PubMed: 34220800
DOI: 10.3389/fimmu.2021.634138 -
Immunity Sep 2022Poor biochemical characteristics have severely hampered the development of the promising malaria transmission-blocking vaccine candidate Pfs48/45. In this issue of...
Poor biochemical characteristics have severely hampered the development of the promising malaria transmission-blocking vaccine candidate Pfs48/45. In this issue of Immunity, McLeod et al. applied structure-guided vaccine design to transform this protein into a stable, high-producing antigen that elicits exceptional blocking antibodies, renewing its promise as a tool to fight malaria.
Topics: Antibodies, Protozoan; Humans; Malaria; Malaria Vaccines; Membrane Glycoproteins; Protozoan Proteins
PubMed: 36103857
DOI: 10.1016/j.immuni.2022.08.013 -
Frontiers in Immunology 2023, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective...
, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from , was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti--specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce -specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after challenge ( 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively ( 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against infection.
Topics: Animals; Mice; Mice, Inbred BALB C; Protozoan Proteins; Protozoan Vaccines; Toxoplasmosis; Immunization; Immunoglobulin G
PubMed: 37122740
DOI: 10.3389/fimmu.2023.1161507 -
Parasitology Research Dec 2023Neospora caninum is an apicomplexan protozoan that causes neosporosis, which has a high economic impact on cattle herds with no available vaccine. During infection, the...
Immunisation with Neospora caninum subunits rsNcSAG4 and rsNcGRA1 (NcSAG4 and NcGRA1 epitopes construct) in BALB/c mice: the profile of the immune response and controlling the vertical transmission.
Neospora caninum is an apicomplexan protozoan that causes neosporosis, which has a high economic impact on cattle herds with no available vaccine. During infection, the secretion of dense granules and the expression of surface antigens play an important role in hosting immunomodulation. However, some epitopes of those antigens are immunogenic, and using these fractions could improve the subunit antigens in vaccine design. This study evaluates the recombinant peptides rsNcGRA1 and rsNcSAG4 derived from NcGRA1 and NcSAG4 native antigens as vaccine candidates produced by a fermentative process in the yeast culture system of Komagataella phaffii strain Km71, confirmed by colony PCR, SDS-PAGE, and western blotting. The assay was conducted in BALB/c mice using the peptides at low (25 μg) and standard (50 μg) dosages in monovalent and combined administrations at three time points with saponin as an adjuvant assessing the immunogenicity by antibodies response and cytokine production. We challenge the females after pregnancy confirmation using 2 × 10 NC-1 tachyzoites previously propagated in Vero cells. We assessed the chronic infection in dams and vertical transmission in the offspring by PCR and histopathology. Mice, especially those immunised with combined peptides and monovalent rsNcGRA1 at a standard dose, controlling the chronic infection in dams with the absence of clinical manifestations, showed an immune response with induction of IgG1, a proper balance between Th1/Th2 cytokines and reduced vertical transmission in the pups. In contrast, dams inoculated with a placebo vaccine showed clinical signs, low-scored brain lesions, augmented chronic infection with 80% positivity, 31% mortality in pups, and 81% vertical transmission. These findings indicate that rsNcGRA1 peptides in monovalent and combined with rsNCSAG4 at standard dose are potential vaccine candidates and improve the protective immune response against neosporosis in mice.
Topics: Animals; Female; Mice; Pregnancy; Antibodies, Protozoan; Antigens, Protozoan; Chlorocebus aethiops; Coccidiosis; Cytokines; Epitopes; Immunity; Infectious Disease Transmission, Vertical; Mice, Inbred BALB C; Neospora; Persistent Infection; Protozoan Vaccines; Vaccination; Vero Cells
PubMed: 38110570
DOI: 10.1007/s00436-023-08020-0 -
Immunology Aug 2021Leishmania is a protozoan parasite that resides in mammalian macrophages and inflicts the disease known as leishmaniasis. Although prevalent in 88 countries, an...
Leishmania is a protozoan parasite that resides in mammalian macrophages and inflicts the disease known as leishmaniasis. Although prevalent in 88 countries, an anti-leishmanial vaccine remains elusive. While comparing the virulent and avirulent L. major transcriptomes by microarray, PCR and functional analyses for identifying a novel virulence-associated gene, we identified LmjF.36.3850, a hypothetical protein significantly less expressed in the avirulent parasite and without any known function. Motif search revealed that LmjF.36.3850 protein shared phosphorylation sites and other structural features with sucrose non-fermenting protein (Snf7) that shuttles virulence factors. LmjF.36.3850 was predicted to bind diacylglycerol (DAG) with energy value similar to PKCα and PKCβ, to which DAG is a cofactor. Indeed, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a DAG analogue, enhanced the phosphorylation of PKCα and PKCβI. We cloned LmjF.36.3850 gene in a mammalian expression vector and primed susceptible BALB/c mice followed by challenge infection. We observed a higher parasite load, comparable antibody response and higher anti-inflammatory cytokines such as IL-4 and IL-10, while expression of major anti-leishmanial cytokine, IFN-γ, remained unchanged in LmjF.36.3850-vaccinated mice. CSA restimulated LN cells from vaccinated mice after challenge infection secreted comparable IL-4 and IL-10 but reduced IFN-γ, as compared to controls. These observations suggest a skewed Th2 response, diminished IFN-γ secreting Th1-T cells and increased central and effector memory subtype of Th2, Th17 and Treg cells in the vaccinated mice. These data indicate that LmjF.36.3850 is a plausible virulence factor that enhances disease-promoting response, possibly by interfering with PKC activation and by eliciting disease-promoting T cells.
Topics: Animals; Antigens, Protozoan; Cells, Cultured; Cloning, Molecular; Cytokines; Gene Expression Profiling; Humans; Leishmania major; Leishmaniasis, Cutaneous; Macrophages; Mice; Mice, Inbred BALB C; Parasite Load; Protozoan Vaccines; T-Lymphocytes, Regulatory; Th2 Cells; Vaccination; Virulence
PubMed: 33764520
DOI: 10.1111/imm.13331 -
EBioMedicine Mar 2019
Topics: Humans; Parasitic Diseases; Protozoan Vaccines; Venezuela
PubMed: 30929743
DOI: 10.1016/j.ebiom.2019.03.039 -
Frontiers in Immunology 2022Malaria transmission blocking vaccines (TBV) aim to induce antibodies that can interrupt development in the mosquito midgut and thereby prevent onward malaria...
Malaria transmission blocking vaccines (TBV) aim to induce antibodies that can interrupt development in the mosquito midgut and thereby prevent onward malaria transmission. A limited number of TBV candidates have been identified and only three (Pfs25, Pfs230 and Pfs48/45) have entered clinical testing. While one of these candidates may emerge as a highly potent TBV candidate, it is premature to determine if they will generate sufficiently potent and sustained responses. It is therefore important to explore novel candidate antigens. We recently analyzed sera from naturally exposed individuals and found that the presence and/or intensity of antibodies against 12 novel putative surface expressed gametocyte antigens was associated with transmission reducing activity. In this study, protein fragments of these novel TBV candidates were designed and heterologously expressed in S2 cells and . Eleven protein fragments, covering seven TBV candidates, were successfully produced. All tested antigens were recognized by antibodies from individuals living in malaria-endemic areas, indicating that native epitopes are present. All antigens induced antigen-specific antibody responses in mice. Two antigens induced antibodies that recognized a native protein in gametocyte extract, and antibodies elicited by four antigens recognized whole gametocytes. In particular, we found that antigen Pf3D7_0305300, a putative transporter, is abundantly expressed on the surface of gametocytes. However, none of the seven novel TBV candidates expressed here induced an antibody response that reduced parasite development in the mosquito midgut as assessed in the standard membrane feeding assay. Altogether, the antigen fragments used in this study did not prove to be promising transmission blocking vaccine constructs, but led to the identification of two gametocyte surface proteins that may provide new leads for studying gametocyte biology.
Topics: Animals; Antibodies, Protozoan; Antigens; Culicidae; Drosophila melanogaster; Malaria; Malaria Vaccines; Mice; Plasmodium falciparum; Protozoan Proteins
PubMed: 35812379
DOI: 10.3389/fimmu.2022.909060 -
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 -
MBio Oct 2021Infection with malaria parasites continues to be a major global public health issue. While current control measures have enabled a significant decrease in morbidity and...
Infection with malaria parasites continues to be a major global public health issue. While current control measures have enabled a significant decrease in morbidity and mortality over the last 20 years, additional tools will be required if we are to progress toward malaria parasite eradication. Malaria vaccine research has focused on the development of subunit vaccines; however, more recently, interest in whole-parasite vaccines has reignited. Whole-parasite vaccines enable the presentation of a broad repertoire of antigens to the immune system, which limits the impact of antigenic polymorphism and genetic restriction of the immune response. We previously reported that whole-parasite vaccines can be prepared using chemically attenuated parasites within intact red blood cells or using killed parasites in liposomes, although liposomes were less immunogenic than attenuated parasites. If they could be frozen or freeze-dried and be made more immunogenic, liposomal vaccines would be ideal for vaccine deployment in areas where malaria is endemic. Here, we develop and evaluate a Plasmodium yoelii liposomal vaccine with enhanced immunogenicity and efficacy due to incorporation of TLR4 agonist, 3D(6-acyl) PHAD, and mannose to target the liposome to antigen-presenting cells. Following vaccination, mice were protected, and strong cellular immune responses were induced, characterized by parasite-specific splenocyte proliferation and a mixed Th1/Th2/Th17 cytokine response. Parasite-specific antibodies were induced, predominantly of the IgG1 subclass. CD4 T cells and gamma interferon were critical components of the protective immune response. This study represents an important development toward evaluation of this whole-parasite blood-stage vaccine in a phase I clinical trial. Malaria is a mosquito-borne infectious disease that is caused by parasites of the genus, . There are seven different spp. that can cause malaria in humans, with P. falciparum causing the majority of the morbidity and mortality. Malaria parasites are endemic in 87 countries and continue to result in >200 million cases of malaria and >400,000 deaths/year, mostly children <5 years of age. Malaria infection initially presents as a flu-like illness but can rapidly progress to severe disease in nonimmune individuals if treatment is not initiated promptly. Existing control strategies for the mosquito vector (insecticides) and parasite (antimalarial drugs) are becoming increasingly less effective due to the development of resistance. While artemisinin combination therapies are frontline treatment for P. falciparum malaria, resistance has been documented in numerous countries. A highly effective malaria vaccine is urgently required to reduce malaria-attributable clinical disease and death and enable progression toward the ultimate goal of eradication.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Erythrocytes; Female; Immunity, Cellular; Immunogenicity, Vaccine; Liposomes; Malaria; Malaria Vaccines; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Plasmodium yoelii; T-Lymphocytes
PubMed: 34663097
DOI: 10.1128/mBio.02657-21