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Clinical and Vaccine Immunology : CVI Jul 2017From experimental models and the analyses of patients, it is well documented that antigen-specific T cells are critical for protection against infection. Effective... (Review)
Review
From experimental models and the analyses of patients, it is well documented that antigen-specific T cells are critical for protection against infection. Effective vaccines require both targeting to the pathogen and an immune stimulant to induce maturation of appropriate immune responses. While a great number of antigens have been examined as vaccine candidates against various species, few have advanced to human or canine clinical trials. With emphasis on antigen expression, in this minireview we discuss some of the vaccine platforms that are currently being explored for the development of vaccines. It is clear that the vaccine platform of choice can have a significant impact upon the level of protection induced by particular antigens, and we provide and highlight some examples for which the vaccine system used has impacted the protective efficacy imparted.
Topics: Adjuvants, Immunologic; Antigens, Protozoan; Drug Carriers; Drug Delivery Systems; Humans; Leishmania; Leishmaniasis; Leishmaniasis Vaccines; T-Lymphocytes
PubMed: 28515135
DOI: 10.1128/CVI.00108-17 -
Communications Biology Aug 2022A vaccine targeting multiple stages of the Plasmodium falciparum parasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of...
A vaccine targeting multiple stages of the Plasmodium falciparum parasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of leading anti-infective P. falciparum pre-erythrocytic vaccines. Pfs230, a sexual-stage P. falciparum surface protein, is currently in trials as the basis for a transmission-blocking vaccine, which inhibits parasite development in the mosquito vector. Here, recombinant full-length CSP and a Pfs230 fragment (Pfs230D1+) are co-displayed on immunogenic liposomes to induce immunity against both infection and transmission. Liposomes contain cobalt-porphyrin phospholipid (CoPoP), monophosphoryl lipid A and QS-21, and rapidly bind His-tagged CSP and Pfs230D1+ upon admixture to form bivalent particles that maintain reactivity with conformational monoclonal antibodies. Use of multicolor fluorophore-labeled antigens reveals liposome binding upon admixture, stability in serum and enhanced uptake in murine macrophages in vitro. Bivalent liposomes induce humoral and cellular responses against both CSP and Pfs230D1+. Vaccine-induced antibodies reduce parasite numbers in mosquito midguts in a standard membrane feeding assay. Mice immunized with liposome-displayed antigens or that passively receive antibodies from immunized rabbits have reduced parasite liver burden following challenge with transgenic sporozoites expressing P. falciparum CSP.
Topics: Animals; Antibodies, Protozoan; Antigens; Liposomes; Malaria Vaccines; Mice; Plasmodium falciparum; Protozoan Proteins; Rabbits; Sporozoites
PubMed: 35915227
DOI: 10.1038/s42003-022-03688-z -
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 Journal of Infectious Diseases Jun 2018
Topics: Animals; Antigens, Protozoan; Epitopes; Humans; Immunization; Malaria Vaccines; Membrane Proteins; Merozoite Surface Protein 1; Merozoites; Parasites
PubMed: 29584870
DOI: 10.1093/infdis/jiy171 -
Poultry Science Jan 2024Avian coccidiosis caused by Eimeria is a serious parasitic disease that poses a threat to the poultry industry. Currently, prevention and treatment mainly rely on the...
Avian coccidiosis caused by Eimeria is a serious parasitic disease that poses a threat to the poultry industry. Currently, prevention and treatment mainly rely on the administration of anticoccidials and live oocyst vaccines. However, the prevalence of drug resistance and the inherent limitations of live vaccines have driven the development of novel vaccines. In this study, the surface protein (Et-SAG14), a previously annotated rhoptry protein (Eten5-B), and a gametocyte phosphoglucomutase (Et-PGM1) were characterized and the vaccine potential of the recombinant proteins were evaluated. Et-SAG14 was dispersed in the form of particles in the sporozoite and merozoite stages, whereas Et-PGM1 was distributed in the apical part of the sporozoite and merozoite stages. The previously annotated rhoptry Eten5-B was found not to be located in the rhoptry but distributed in the cytoplasm of sporozoites and merozoites. Immunization with rEten5-B significantly elevated host interferon gamma (IFN-γ) and interleukin 10 (IL-10) transcript levels and exhibited moderate anticoccidial effects with an anticoccidial index (ACI) of 161. Unexpectedly, both recombinant Et-SAG14 and Et-PGM1 immunization significantly reduced host IFN-γ and IL-10 transcription levels, and did not show protection against E. tenella challenge (ACI < 80). These results suggest that the rEten5-B protein can trigger immune protection against E. tenella and may be a potential and effective subunit vaccine for the control of coccidiosis in poultry.
Topics: Animals; Eimeria tenella; Interleukin-10; Chickens; Recombinant Proteins; Coccidiosis; Sporozoites; Interferon-gamma; Vaccines; Poultry Diseases; Protozoan Vaccines
PubMed: 37980744
DOI: 10.1016/j.psj.2023.103234 -
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 -
Parasites & Vectors Feb 2018Tropical theileriosis is widely distributed from North Africa to East Asia. It is a tick-borne disease caused by Theileria annulata, an obligate two-host intracellular...
Isolation and purification of glycosylphosphatidylinositols (GPIs) in the schizont stage of Theileria annulata and determination of antibody response to GPI anchors in vaccinated and infected animals.
BACKGROUND
Tropical theileriosis is widely distributed from North Africa to East Asia. It is a tick-borne disease caused by Theileria annulata, an obligate two-host intracellular protozoan parasite of cattle. Theileria annulata use leukocytes and red blood cells for completion of the life-cycle in mammalian hosts. The stage of Theileria annulata in monocytes and B lymphocytes of cattle is an important step in pathogenicity and diagnosis of the disease. Glycosylphosphatidylinositols (GPIs) are a distinct class of glycolipid structures found in eukaryotic cells and are implicated in several biological functions. GPIs are particularly abundant in protozoan parasites, where they are found as free glycolipids or attached to proteins in the plasma membrane.
RESULTS
In this study we first isolated and purified schizonts of Theileria annulata from infected leukocytes in Theileria annulata vaccine cell line (S15) by aerolysin-percoll technique. Then, the free GPIs of schizont stage and isolated GPI from cell membrane glycoproteins were purified by high performance liquid chromatography (HPLC) and confirmed by gas chromatography-mass spectrometry (GC-MS). Furthermore, enzyme linked immunosorbent assay (ELISA) on the serum samples obtained from naturally infected, as well as Theileria annulata-vaccinated animals, confirmed a significant (P < 0.01) high level of anti-GPI antibody in their serum.
CONCLUSIONS
The results presented in this study show, to our knowledge for the first time, the isolation of GPI from the schizont stage of Theileria annulata and demonstrate the presence of anti-GPI antibody in the serum of naturally infected as well as vaccinated animals. This finding is likely to be valuable in studies aimed at the evaluation of chemically structures of GPIs in the schizont stage of Theileria annulata and also for pathogenicity and immunogenicity studies with the aim to develop GPI-based therapies or vaccines.
Topics: Animals; Antibodies, Protozoan; Antibody Formation; Cattle; Cattle Diseases; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Gas Chromatography-Mass Spectrometry; Glycosylphosphatidylinositols; Leukocytes; Protozoan Vaccines; Schizonts; Theileria annulata; Theileriasis
PubMed: 29409517
DOI: 10.1186/s13071-018-2651-9 -
The Lancet. Infectious Diseases May 2024The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to...
BACKGROUND
The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa.
METHODS
We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR) and ranges from 3% to 65% PfPR.
FINDINGS
Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR.
INTERPRETATION
Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa.
FUNDING
The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.
Topics: Humans; Cost-Benefit Analysis; Malaria Vaccines; Malaria, Falciparum; Burkina Faso; Models, Theoretical; Child, Preschool; Public Health; Plasmodium falciparum; Child; Protozoan Proteins; Antibodies, Protozoan; Vaccine Efficacy; Infant; Male; Female
PubMed: 38342107
DOI: 10.1016/S1473-3099(23)00816-2 -
International Journal For Parasitology Mar 2018East Coast fever is a lymphoproliferative disease caused by the tick-borne protozoan parasite Theileria parva. The sporozoite stage of this parasite, harboured and...
East Coast fever is a lymphoproliferative disease caused by the tick-borne protozoan parasite Theileria parva. The sporozoite stage of this parasite, harboured and released from the salivary glands of the tick Rhipicephalus appendiculatus during feeding, invades and establishes infection in bovine lymphocytes. Blocking this initial stage of invasion presents a promising vaccine strategy for control of East Coast fever and can in part be achieved by targeting the major sporozoite surface protein p67. To support research on the biology of T. parva and the identification of additional candidate vaccine antigens, we report on the sporozoite proteome as defined by LC-MS/MS analysis. In total, 4780 proteins were identified in an enriched preparation of sporozoites. Of these, 2007 were identified as T. parva proteins, representing close to 50% of the total predicted parasite proteome. The remaining 2773 proteins were derived from the tick vector. The identified sporozoite proteins include a set of known T. parva antigens targeted by antibodies and cytotoxic T cells from cattle that are immune to East Coast fever. We also identified proteins predicted to be orthologs of Plasmodium falciparum sporozoite surface molecules and invasion organelle proteins, and proteins that may contribute to the phenomenon of bovine lymphocyte transformation. Overall, these data establish a protein expression profile of T. parva sporozoites as an important starting point for further study of a parasitic species which has considerable agricultural impact.
Topics: Animals; Antigens, Protozoan; Arachnid Vectors; Cattle; Cattle Diseases; Chromatography, Liquid; Nymph; Proteome; Protozoan Proteins; Protozoan Vaccines; Rhipicephalus; Sporozoites; Tandem Mass Spectrometry; Theileria parva; Theileriasis; Tick-Borne Diseases
PubMed: 29258832
DOI: 10.1016/j.ijpara.2017.09.007