AbstractBackgroundSand flies vector several human pathogens, including Leishmania species, which cause leishmaniases. A leishmaniasis vaccine does not yet exist, so the most common prevention strategies involve personal protection and insecticide spraying. However, insecticides can impact non-target organisms and are becoming less effective because of the evolution of resistance. An alternative control strategy is the attract-and-kill approach, where the vector is lured to a lethal trap, ideally located in oviposition sites that will attract gravid females. Oviposition traps containing attractive microbes have proven successful for the control of some mosquito populations but have not been developed for sand flies. Gravid female sand flies lay their eggs in decomposing organic matter on which the larvae feed and develop. Studies have demonstrated that gravid females are particularly attracted to larval conditioned (containing eggs and larvae) and aged rearing substrates. An isolate-based study has provided some evidence that bacteria play a role in the attraction of sand flies to conditioned substrates. However, the overall bacterial community structure of conditioned and aged substrates and how they change over time has not been investigated.MethodsThe goal of this study was to characterize the bacterial communities of rearing and oviposition substrates that have been shown to vary in attractiveness to gravid sand flies in previous behavioral studies. Using 16S rRNA amplicon sequencing we determined the bacterial composition in fresh, aged, and larval-conditioned substrates at four time points representing the main life-cycle stages of developing sand flies. We compared the diversity, presence, and abundance of taxa across substrate types and time points in order to identify how aging and larval-conditioning impact bacterial community structure.ResultsWe found that the bacterial communities significantly change within and between substrates over time. We also identified bacteria that might be responsible for attraction to conditioned and aged substrates, which could be potential candidates for the development of attract-and-kill strategies for sand flies.ConclusionThis study demonstrated that both aging and larval conditioning induce shifts in the bacterial communities of sand fly oviposition and rearing substrates, which may explain the previously observed preference of gravid female sand flies to substrates containing second/third-instar larvae (conditioned) and substrates aged the same amount of time without larvae (aged).Graphical Abstract

2022-07-01·Vaccine

Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

Article

作者: Flóro E Silva, Marina ; Fernanda Araújo, Thalita ; Ruiz Abánades, Daniel ; Esteves Zorgi, Nahiara ; Giorgio, Selma ; Janaína Soares Rocha, Francisca ; Augusto Sanches Roque, Guilherme

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN - γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.

2020-09-01·European Journal of Pharmaceutical Sciences2区 · 医学

Exploring membrane proteins of Leishmania major to design a new multi-epitope vaccine using immunoinformatics approach

2区 · 医学

Article

作者: Mohammadi, Elyas ; Ghanbariasad, Ali ; Rabienia, Mahsa ; Farjadfar, Akbar ; Roudbari, Zahra ; Mortazavidehkordi, Nahid ; Abdollahi, Abbas

Leishmaniasis is one of the major global endemic diseases. Among all the different forms of the disease, cutaneous Leishmaniasis has the highest prevalence worldwide. Treatment with current drugs has not had a significant effect on the improvement of the disease. An attempt to replace an appropriate vaccine that can stimulate host cellular immunity and induce the response of Major histocompatibility complex I (MHCI) and Major histocompatibility complex II (MHCII) against Leishmania is essential. Vaccine production remains a challenge despite the use of different antigens for vaccination against Leishmania major. Hence, we were used the immunoinformatics approach to design a new multi-epitope vaccine against L. major using immunogenic outer membrane proteins. Helper T-lymphocyte (HTL) and Cytotoxic T lymphocyte (CTL) epitopes were predicted and for final confirmation of the selected epitopes, docking analysis, and molecular dynamics simulation was performed. Then, GDGDG linker and profilin adjuvant were added to enhance the immunity of vaccines. The designed vaccine was evaluated in terms of molecular weight, PI, immunogenicity, and allergenicity. Moreover, the secondary and three-dimensional structure of the final construct was identified. In silico cloning approach was carried out to improve expression of the vaccine construct. Finally, molecular docking, followed by molecular dynamic was performed to determine the interaction between multi-epitope vaccine and TLR11. We hope that the designed vaccine can be a good candidate for the development of cutaneous leishmaniasis vaccine. but its effectiveness should be assessed in vivo.

100 项与 Visceral leishmaniasis vaccine (IDRI) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
内脏利什曼病	临床1期	印度	Gennova Biopharmaceuticals Ltd.	-
内脏利什曼病	临床1期	美国	Infectious Disease Research Institute	-
内脏利什曼病	临床1期	印度	Zydus Lifesciences Ltd.	-