Immunization against a Conserved Surface Polysaccharide Stimulates Bovine Antibodies with Opsonic Killing Activity but Does Not Protect against Babesia bovis Challenge

Arthropod-borne apicomplexan pathogens remain a great concern and challenge for disease control in animals and humans. In order to prevent Babesia infection, the discovery of antigens that elicit protective immunity is essential to establish approaches to stop disease dissemination. In this study, we determined that poly-N-acetylglucosamine (PNAG) is conserved among tick-borne pathogens including B. bovis, B. bigemina, B. divergens, B. microti, and Babesia WA1. Calves immunized with synthetic ß-(1→6)-linked glucosamine oligosaccharides conjugated to tetanus toxoid (5GlcNH2-TT) developed antibodies with in vitro opsonophagocytic activity against Staphylococcus aureus. Sera from immunized calves reacted to B. bovis. These results suggest strong immune responses against PNAG. However, 5GlcNH2-TT-immunized bovines challenged with B. bovis developed acute babesiosis with the cytoadhesion of infected erythrocytes to brain capillary vessels. While this antigen elicited antibodies that did not prevent disease, we are continuing to explore other antigens that may mitigate these vector-borne diseases for the cattle industry.

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Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

Current Medicinal Chemistry ◽

10.2174/0929867325666181105121146 ◽

2019 ◽

Vol 26 (16) ◽

pp. 2974-2986 ◽

Cited By ~ 4

Author(s):

Kwang-sun Kim

Keyword(s):

New Host ◽

In Vivo Models ◽

Vector Borne Diseases ◽

Novel Drugs ◽

Huge Impact ◽

Tick Borne Disease ◽

Vector Borne ◽

Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

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Analysis of the Role of TpUB05 Antigen from Theileria parva in Immune Responses to Malaria in Humans Compared to Its Homologue in Plasmodium falciparum the UB05 Antigen

Pathogens ◽

10.3390/pathogens9040271 ◽

2020 ◽

Vol 9 (4) ◽

pp. 271

Author(s):

Jerome Nyhalah Dinga ◽

Stephanie Numenyi Perimbie ◽

Stanley Dobgima Gamua ◽

Francis N. G. Chuma ◽

Dieudonné Lemuh Njimoh ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Immune Responses ◽

Protective Immunity ◽

Vaccine Development ◽

Theileria Parva ◽

Peripheral Blood Mononuclear ◽

Significant Difference ◽

First Time

Despite the amount of resources deployed and the technological advancements in molecular biology, vaccinology, immunology, genetics, and biotechnology, there are still no effective vaccines against malaria. Immunity to malaria is usually seen to be species- and/or strain-specific. However, there is a growing body of evidence suggesting the possibility of the existence of cross-strain, cross-species, and cross-genus immune responses in apicomplexans. The principle of gene conservation indicates that homologues play a similar role in closely related organisms. The homologue of UB05 in Theileria parva is TpUB05 (XP_763711.1), which has been tested and shown to be associated with protective immunity in East Coast fever. In a bid to identify potent markers of protective immunity to aid malaria vaccine development, TpUB05 was tested in malaria caused by Plasmodium falciparum. It was observed that TpUB05 was better at detecting antigen-specific antibodies in plasma compared to UB05 when tested by ELISA. The total IgG raised against TpUB05 was able to block parasitic growth in vitro more effectively than that raised against UB05. However, there was no significant difference between the two study antigens in recalling peripheral blood mononuclear cell (PBMC) memory through IFN-γ production. This study suggests, for the first time, that TpUB05 from T. parva cross-reacts with UB05 from P. falciparum and is a marker of protective immunity in malaria. Hence, TpUB05 should be considered for possible development as a potential subunit vaccine candidate against malaria.

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Analysis of the role of TpUB05 antigen from Theileria parva in immune responses to malaria in humans compared to its homologue in Plasmodium falciparum; UB05 antigen

10.21203/rs.2.16899/v2 ◽

2019 ◽

Author(s):

Jerome Nyhalah Dinga ◽

Stanley Dobgima Gamua ◽

Stephanie Numenyi Perimbie ◽

Francis N. G. Chuma ◽

Dieudonné Lemuh Njimoh ◽

...

Keyword(s):

Immune Responses ◽

Protective Immunity ◽

Vaccine Development ◽

Ex Vivo ◽

Growth Inhibition Assay ◽

Potential Marker ◽

As Species ◽

Potential Vaccine ◽

First Time

Abstract Background: Despite the amount of resources deployed and technological advancements in Molecular Biology, vaccinology, immunology, genetics, and biotechnology, there is still no effective vaccines against malaria. Immunity to either malaria or East Coast fever is usually seen as species- and/or strain-specific. But there is growing body of evidence suggesting the possibility of the existence of cross strain, cross species and cross genus immune responses in apicomplexans. The principle of gene conservations indicates that homologues play similar role in closely related organisms. UB05 antigen (XP_001347656.2) from P. falciparum is part of chimeric UB05-09 antigen; a potential vaccine candidate has been demonstrated to be a marker of protective immunity in malaria. The homologue of UB05 in T. parva is TpUB05 (XP_763711.1) which was also tested and shown to be a potential marker of protective immunity in ECF as well. In a bid to identify potent markers of protective immunity to aid malaria vaccine development, TpUB05 was tested in malaria caused by P. falciparum . Results: It was observed that TpUB05 provoked stronger immune responses in malaria compared to UB05 antigen as tested using ELISA, ex-vivo ELISpot assay and in vitro growth inhibition assay. Conclusion: This study suggests for the first time that TpUB05 from T. parva is a better marker of protective immunity in malaria compared to its homologue UB05 from P. falciparum .

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Expression of MicroRNA of Macrophages Infected with Attenuated Leishmania major Parasite

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0041-1724021 ◽

2021 ◽

Vol 16 (03) ◽

pp. 106-110

Author(s):

Mohammad Hossein Feiz Haddad ◽

Hossein Rezvan ◽

Alireza Nourian ◽

Habib Habibpour

Keyword(s):

Real Time ◽

Leishmania Major ◽

Host Cells ◽

Control Group ◽

Vector Borne Diseases ◽

Intracellular Parasites ◽

Significant Difference ◽

Infected Cells ◽

Vector Borne

Abstract Objective Leishmaniasis has been proposed as one of the neglected vector-borne diseases due to an obligate intracellular parasite of the genus Leishmania. MicroRNAs (miRNAs) with a length of 22-nucleotide are known as the noncoding small RNAs. MiRNAs contribute to many biological and cellular approaches. Therefore, the present study evaluated expressing mmu-miR-721, mmu-miR-294–3p, mmu-miR-155–3p, and mmu-miR-30a in murine macrophages infected with attenuated Leishmania major parasites on 3 days after infection. Methods Attenuated promastigotes have been achieved after 20 passages of Leishmania major parasites. Cell line J774A.1 (murine macrophage) has been used for in vitro experiments. The stationary phase of attenuated L. major promastigotes has been chosen to infect the cells, and then their incubation has been performed with 5% CO2 at 37°C for 3 days. The real-time polymerase chain reaction (PCR) has also been performed with SYBR Green master-mix Kit for measuring the level of mmu-miR-721, mmu-miR-294–3p, mmu-miR-30a, and mmu-miR-155-3p expression. Uninfected macrophages have been considered as a control group. Results Real-time PCR demonstrated overexpression of mmu-miR-155-3p, mmu-miR-294–3p, and, mmu-miR-721 in the infected cells with Leishmania parasites after 3 days. Results showed no statistically significant difference in the mmu-miR-30a expression between infected macrophages and the uninfected control group. Conclusion Our findings suggested the significant contribution of the alterations in the miRNA levels to the regulation of macrophage functions following the creation of intracellular parasites like Leishmania. These data could help to understand better the genes' expression in the host cells in the course of leishmaniasis.

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Revealing the molecular interplay of curcumin as Culex pipiens Acetylcholine esterase 1 (AChE1) inhibitor

Scientific Reports ◽

10.1038/s41598-021-96963-8 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Priyashi Rao ◽

Dweipayan Goswami ◽

Rakesh M. Rawal

Keyword(s):

Culex Pipiens ◽

Early Stage ◽

Homology Modelling ◽

Acetylcholine Esterase ◽

Ache Inhibition ◽

Vector Borne Diseases ◽

Computational Screening ◽

Vector Borne

AbstractEmergence of vector borne diseases has continued to take toll on millions of lives since its inception. The use of insecticides began as vector control strategy in the early 1900’s but the menace of insects is still prevalent. Additionally, the inadequate use of organophosphates and carbamates which target acetylcholine esterase (AChE), are known to develop resistance amongst vectors of transmission and are toxic to humans. In this study, extensive computational screening was performed using homology modelling, molecular docking, molecular dynamics (MD) simulation and free energy change calculation, which highlighted curcumin as a lead molecule out of ~ 1700 phytochemicals against Culex pipiens AChE. In vivo larvicidal activity was carried out along with in vivo and in vitro AChE inhibition assay to determine the biochemical efficacy of curcumin. Our study reveals that curcumin induces mortality in Cx. pipiens at an early stage of its life cycle by AChE inhibition. This also underlines the use of curcumin as a coming-age natural product insecticide.

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Immunization of mice against Trichinella spiralis and T. britovi using excretory and secretory antigens

Journal of Helminthology ◽

10.1017/s0022149x00015765 ◽

1997 ◽

Vol 71 (2) ◽

pp. 109-112 ◽

Cited By ~ 5

Author(s):

P.K. Goyal ◽

F. Bolas-Fernandez ◽

D. Wakelin

Keyword(s):

Immune Responses ◽

Protective Immunity ◽

Trichinella Spiralis ◽

Antibody Responses ◽

Current Understanding ◽

T Helper ◽

T Helper 2 ◽

Mesenteric Node ◽

Specific Igg

AbstractImmune responses to immunization and infection with Trichinella spiralis and T. britovi were studied in NIH high-responder mice. Overall it was shown that T. britovi was the more immunogenic, immunization and challenge with this species giving greater host-protective immunity. This greater immunogenicity was reflected in higher proliferative responses when mesenteric node lymphocytes (MLNC) from immunized mice were restimulated with T. britovi antigens in vitro and in higher levels of T helper 2 (Th2) lymphocyte-dependent specific IgG1 antibody responses against this species. MLNC from mice immunized against T. britovi released more IL-5 when restimulated in vitro, again suggesting a greater T helper 2 subset response, but after infection the highest levels of IL-5 were recorded from MLNC taken from T. spiralis challenged mice. These data are discussed in relation to current understanding of immunological differences between species and isolates of the genus Trichinella.

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Inclusion Complexes of Citronella Oil with β-Cyclodextrin for Controlled Release in Biofunctional Textiles

Polymers ◽

10.3390/polym10121324 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1324 ◽

Cited By ~ 5

Author(s):

Manuel Lis ◽

Óscar García Carmona ◽

Carlos García Carmona ◽

Fabricio Maestá Bezerra

Keyword(s):

Controlled Release ◽

Release Mechanism ◽

Ultraviolet Region ◽

Skin Damage ◽

Vector Borne Diseases ◽

Citronella Oil ◽

Vector Borne ◽

Toxic Reactions ◽

Crosslinking Agents

Biofunctional textiles with integrated drug-delivery systems can help in the fight against vector-borne diseases. The use of repellent agents derived from plants and oils is an alternative to DEET (N,N-diethyl-m-methylbenzamide), which has disadvantages that include toxic reactions and skin damage. However, some researchers report that oils can be ineffective due to reasons related to uncontrolled release. In this work, the mechanism of control of citronella oil (OC) complexed with β-cyclodextrin (βCD) on cotton (COT) and polyester (PES) textiles was investigated. The results obtained reveal that finishing cotton and polyester with β-cyclodextrin complexes allows for control of the release mechanism of the drug from the fabric. To assess the complexes formed, optical microscopy, SEM, and FTIR were carried out; the yield of complex formation was obtained by spectroscopy in the ultraviolet region; and controlled release was performed in vitro. Oil complexation with βCD had a yield of 63.79%, and it was observed that the release, which was in seconds, moved to hours when applied to fabrics. The results show that complexes seem to be a promising basis when it comes to immobilizing oils and controlling their release when modified with chemical crosslinking agents.

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Vector Specificity of Arbovirus Transmission

Frontiers in Microbiology ◽

10.3389/fmicb.2021.773211 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marine Viglietta ◽

Rachel Bellone ◽

Adrien Albert Blisnick ◽

Anna-Bella Failloux

Keyword(s):

Immune Responses ◽

Molecular Mechanisms ◽

Mosquito Species ◽

Pathogen Transmission ◽

Dynamic Nature ◽

Vector Borne Diseases ◽

Vector Specificity ◽

Vector Borne ◽

Appropriate Practices ◽

Large Distribution

More than 25% of human infectious diseases are vector-borne diseases (VBDs). These diseases, caused by pathogens shared between animals and humans, are a growing threat to global health with more than 2.5 million annual deaths. Mosquitoes and ticks are the main vectors of arboviruses including flaviviruses, which greatly affect humans. However, all tick or mosquito species are not able to transmit all viruses, suggesting important molecular mechanisms regulating viral infection, dissemination, and transmission by vectors. Despite the large distribution of arthropods (mosquitoes and ticks) and arboviruses, only a few pairings of arthropods (family, genus, and population) and viruses (family, genus, and genotype) successfully transmit. Here, we review the factors that might limit pathogen transmission: internal (vector genetics, immune responses, microbiome including insect-specific viruses, and coinfections) and external, either biotic (adult and larvae nutrition) or abiotic (temperature, chemicals, and altitude). This review will demonstrate the dynamic nature and complexity of virus–vector interactions to help in designing appropriate practices in surveillance and prevention to reduce VBD threats.

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LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor

Journal of Experimental Medicine ◽

10.1084/jem.20121466 ◽

2012 ◽

Vol 210 (1) ◽

pp. 5-13 ◽

Cited By ~ 59

Author(s):

Xin-Jiang Lu ◽

Jiong Chen ◽

Chao-Hui Yu ◽

Yu-Hong Shi ◽

Yu-Qing He ◽

...

Keyword(s):

Immune Responses ◽

Protective Immunity ◽

Polymorphonuclear Neutrophils ◽

Bacterial Sepsis ◽

Bacterial Killing ◽

Improved Outcome ◽

Multifunctional Cytokine

Leukocyte cell–derived chemotaxin 2 (LECT2) is a multifunctional cytokine and reduced plasma levels were found in patients with sepsis. However, precise functions and mechanisms of LECT2 remain unclear. The aim of the present study was to determine the role of LECT2 in modulating immune responses using mouse sepsis models. We found that LECT2 treatment improved outcome in mice with bacterial sepsis. Macrophages (MΦ), but not polymorphonuclear neutrophils, mediated the beneficial effect of LECT2 on bacterial sepsis. LECT2 treatment could alter gene expression and enhance phagocytosis and bacterial killing of MΦ in vitro. CD209a was identified to specifically interact with LECT2 and mediate LECT2-induced MΦ activation. CD209a-expressing MΦ was further confirmed to mediate the effect of LECT2 on sepsis in vivo. Our data demonstrate that LECT2 improves protective immunity in bacterial sepsis, possibly as a result of enhanced MΦ functions via the CD209a receptor. The modulation of MΦ functions by LECT2 may serve as a novel potential treatment for sepsis.

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Blocking the Transmission of a Noncirculative Vector-Borne Plant Pathogenic Bacterium

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-02-16-0032-r ◽

2016 ◽

Vol 29 (7) ◽

pp. 535-544 ◽

Cited By ~ 8

Author(s):

Fabien Labroussaa ◽

Adam R. Zeilinger ◽

Rodrigo P. P. Almeida

Keyword(s):

Cell Adhesion ◽

Plant Pathogens ◽

Control Strategies ◽

Hypothetical Protein ◽

Insect Vector ◽

Bacterial Populations ◽

Vector Borne Diseases ◽

Nontarget Effects ◽

Vector Borne

The successful control of insect-borne plant pathogens is often difficult to achieve due to the ecologically complex interactions among pathogens, vectors, and host plants. Disease management often relies on pesticides and other approaches that have limited long-term sustainability. To add a new tool to control vector-borne diseases, we attempted to block the transmission of a bacterial insect-transmitted pathogen, the bacterium Xylella fastidiosa, by disrupting bacteria–insect vector interactions. X. fastidiosa is known to attach to and colonize the cuticular surface of the mouthparts of vectors; a set of recombinant peptides was generated and the chemical affinities of these peptides to chitin and related carbohydrates was assayed in vitro. Two candidates, the X. fastidiosa hypothetical protein PD1764 and an N-terminal region of the hemagglutinin-like protein B (HxfB) showed affinity for these substrates. These proteins were provided to vectors via an artificial diet system in which insects acquire X. fastidiosa, followed by an inoculation access period on plants under greenhouse conditions. Both PD1764 and HxfAD1-3 significantly blocked transmission. Furthermore, bacterial populations within insects over a 10-day period demonstrated that these peptides inhibited cell adhesion to vectors but not bacterial multiplication, indicating that the mode of action of these peptides is restricted to limiting cell adhesion to insects, likely via competition for adhesion sites. These results open a new venue in the search for sustainable disease-control strategies that are pathogen specific and may have limited nontarget effects.

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