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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 -
Microbiology Spectrum Jan 2024, an obligate intracellular eukaryotic parasite, can infect about one-third of the world's population. One vaccine, Toxovax, has been developed and licensed...
, an obligate intracellular eukaryotic parasite, can infect about one-third of the world's population. One vaccine, Toxovax, has been developed and licensed commercially; however, it is only used in the sheep industry to reduce the losses caused by congenital toxoplasmosis. Various other vaccine approaches have been explored, including excretory secretion antigen vaccines, subunit vaccines, epitope vaccines, and DNA vaccines. However, current research has not yet developed a safe and effective vaccine for . Here, we generated an mRNA vaccine candidate against . We investigated the efficacy of vaccination with a novel identified candidate, TGGT1_278620, in a mouse infection model. We screened -derived protective antigens at the genome-wide level, combined them with mRNA-lipid nanoparticle vaccine technology against , and investigated immune-related factors and mechanisms. Our findings might contribute to developing vaccines for immunizing humans and animals against .
Topics: Humans; Mice; Animals; Sheep; mRNA Vaccines; Mice, Inbred BALB C; Protozoan Proteins; Immunity, Cellular; Toxoplasmosis; Toxoplasma; Vaccines, DNA; Antigens, Protozoan
PubMed: 38038457
DOI: 10.1128/spectrum.02866-23 -
Malaria Journal Sep 2023After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and... (Review)
Review
After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.
Topics: Pregnancy; Child; Humans; Adult; Female; Pandemics; COVID-19; Malaria; Malaria Vaccines; Autopsy
PubMed: 37726804
DOI: 10.1186/s12936-023-04714-z -
Cell Host & Microbe Dec 2023Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines...
Vivax malaria has long been thought to be absent from sub-Saharan Africa owing to the high proportion of individuals lacking the Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed to be the main pathway used by merozoites to invade reticulocytes. However, the increasing number of reports of vivax malaria cases in genotypically Duffy-negative (DN) individuals has raised questions regarding the P. vivax invasion pathway(s). Here, we show that a subset of DN erythroblasts transiently express DARC during terminal erythroid differentiation and that P. vivax merozoites, irrespective of their origin, can invade DARC+ DN erythroblasts. These findings reveal that a large number of DN individuals may represent a silent reservoir of deep P. vivax infections at the sites of active erythropoiesis with low or no parasitemia, and it may represent an underestimated biological problem with potential clinical consequences in sub-Saharan Africa.
Topics: Humans; Malaria, Vivax; Antigens, Protozoan; Protozoan Proteins; Plasmodium vivax; Erythrocytes; Duffy Blood-Group System
PubMed: 38056460
DOI: 10.1016/j.chom.2023.11.007 -
Frontiers in Cellular and Infection... 2024
Topics: Antigens, Protozoan; Malaria; Humans; Plasmodium; Animals; Malaria Vaccines
PubMed: 38686096
DOI: 10.3389/fcimb.2024.1408366 -
Malaria Journal Jan 2024Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections... (Review)
Review
Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections and over 600,000 deaths across 85 countries. In the ongoing battle against malaria, a promising development has emerged with the endorsement by the World Health Organization (WHO) of the R21/Matrix-M Malaria Vaccine. Developed through a collaboration between the University of Oxford and Novavax, this vaccine has demonstrated remarkable efficacy, reaching 77% effectiveness in Phase 2 clinical trials. It is designed to be low-dose, cost-effective, and accessible, with approval for use in children under three years old. This perspective paper critically examines the R21/Matrix-M malaria vaccine, its development, potential impact on global malaria eradication efforts, and the challenges and opportunities it presents.
Topics: Child; Humans; Child, Preschool; Malaria Vaccines; Malaria
PubMed: 38216923
DOI: 10.1186/s12936-024-04846-w -
Nature Jan 2024The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5...
The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5 (refs. ), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies or nanobodies against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies, binds to the PfCSS-PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.
Topics: Animals; Humans; Antibodies, Neutralizing; Antigens, Protozoan; Cryoelectron Microscopy; Disulfides; Erythrocytes; Malaria Vaccines; Malaria, Falciparum; Merozoites; Multiprotein Complexes; Parasites; Plasmodium falciparum; Protozoan Proteins
PubMed: 38123677
DOI: 10.1038/s41586-023-06856-1 -
ACS Omega Nov 2023African trypanosomiasis is a vector-borne disease of animals and humans in the tsetse fly belt of Africa. ("nagana") is the most pathogenic trypanosome in livestock and...
African trypanosomiasis is a vector-borne disease of animals and humans in the tsetse fly belt of Africa. ("nagana") is the most pathogenic trypanosome in livestock and causes high morbidity and mortality rates among cattle. In the absence of effective preventative vaccines, the management of trypanosomiasis relies on chemoprophylaxis and/or -therapy. However, the trypanocides in clinical use exhibit poor oral bioavailability and toxicity, and therapeutic failures occur because of resistant strains. Because nitrofurantoin displayed, in addition to its clinical use, promising antiparasitic activity, the current study was conducted to evaluate the trypanocidal activity and preliminary treatment efficacy of previously synthesized nitrofuranylazines. The trypanocidal activity of these nitrofuran derivatives varied among the evaluated trypanosome species; however, strain IL3000 was more susceptible than other animal and human trypanosomes. The nitrofurylazines (IC 0.04 μM; SI > 7761) and (IC 0.03 μM; SI > 9542) as well as the nitrothienylazine (IC 0.04 μM; SI 232), with nanomolar IC values, were revealed as early antitrypanosomal leads. Although these derivatives showed strong trypanocidal activity , no treatment efficacy was observed in IL3000 infected mice after both oral and intraperitoneal administration in a preliminary study. This was attributed to the poor solubility of the test compounds in the testing media. Indeed, a challenge in drug discovery is finding a balance between the physicochemical properties of a drug candidate, particularly lipophilicity and water solubility, and maintaining adequate potency to provide an effective dose. Hence, future chemical modifications may be required to generate lead-like to lead-like nitrofuranylazines that possess optimal physicochemical and pharmacokinetic properties while retaining and, ultimately, trypanocidal efficacy.
PubMed: 38024678
DOI: 10.1021/acsomega.3c06508 -
The Journal of Infectious Diseases Sep 2023Studies have demonstrated the protective role of antibodies against malaria. Young children are known to be particularly vulnerable to malaria, pointing to the evolution...
BACKGROUND
Studies have demonstrated the protective role of antibodies against malaria. Young children are known to be particularly vulnerable to malaria, pointing to the evolution of naturally acquired clinical immunity over time. However, whether changes in antibody functionality track with the acquisition of naturally acquired malaria immunity remains incompletely understood.
METHODS
Using systems serology, we characterized sporozoite- and merozoite-specific antibody profiles of uninfected Malian children before the malaria season who differed in their ability to control parasitemia and fever following Plasmodium falciparum (Pf) infection. We then assessed the contributions of individual traits to overall clinical outcomes, focusing on the immunodominant sporozoite CSP and merozoite AMA1 and MSP1 antigens.
RESULTS
Humoral immunity evolved with age, with an expansion of both magnitude and functional quality, particularly within blood-stage phagocytic antibody activity. Moreover, concerning clinical outcomes postinfection, protected children had higher antibody-dependent neutrophil activity along with higher levels of MSP1-specific IgG3 and IgA and CSP-specific IgG3 and IgG4 prior to the malaria season.
CONCLUSIONS
These data point to the natural evolution of functional humoral immunity to Pf with age and highlight particular antibody Fc-effector profiles associated with the control of malaria in children, providing clues for the design of next-generation vaccines or therapeutics.
Topics: Animals; Humans; Child; Child, Preschool; Plasmodium falciparum; Merozoite Surface Protein 1; Neutrophils; Antigens, Protozoan; Antibodies, Protozoan; Malaria; Malaria, Falciparum; Adaptive Immunity; Merozoites; Immunoglobulin G; Autoantibodies
PubMed: 37150885
DOI: 10.1093/infdis/jiad115 -
Malaria Journal May 2024Malaria vaccine introduction in endemic countries is a game-changing milestone in the fight against the disease. This article examines the inequity in the global... (Review)
Review
Malaria vaccine introduction in endemic countries is a game-changing milestone in the fight against the disease. This article examines the inequity in the global pharmaceutical research, development, manufacturing, and trade landscape. The role of inequity in hindering progress towards malaria elimination is explored. The analysis finds that transformational changes are required to create an equity-enabling environment. Addressing the inequity is critical to maximizing the public health impact of vaccines and attaining sustainability. Avenues to catalyze progress by leveraging malaria vaccines and messenger ribonucleic acid (mRNA) technology are discussed.
Topics: Humans; Disease Eradication; Global Health; Malaria; Malaria Vaccines; Pharmaceutical Research; mRNA Vaccines; Africa
PubMed: 38711053
DOI: 10.1186/s12936-024-04972-5