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Biology subjects

Mahmoudi, M.

Publications and source records attributed to Mahmoudi, M..

3 recordsLinked to original sources

Development and characterization of influenza M2 ectodomain and/or HA stalk-based DC-targeting vaccines for different influenza infections

A universal influenza vaccine is required for broad protection against influenza infection. Here, we revealed the efficacy of novel influenza vaccine candidates based on Ebola glycoprotein (EboGP) DC-targeting domain (E{Delta}M) fusion protein technology. We fused influenza hemagglutinin stalk (HAcs) and extracellular matrix protein (M2e) or four copies of M2e (referred to as tetra M2e (tM2e)) with E{Delta}M to generate E{Delta}M-HM2e or E{Delta}M-tM2e, respectively, and revealed that E{Delta}M facilitates DC/macrophage targeting in vitro. In a mouse study, E{Delta}M-HM2e- or E{Delta}M-tM2e-pseudotyped viral particles (PVPs) induced significantly higher titers of anti-HA and/or anti-M2e antibodies. We also developed recombinant vesicular stomatitis virus (rVSV)-E{Delta}M-HM2e and rVSV-E{Delta}M-tM2e vaccines that resulted in rapid and potent induction of HA and/or M2 antibodies in mouse sera and mucosa. Importantly, vaccination protects mice from influenza H1N1 and H3N2 challenges. Taken together, our study suggests that recombinant rVSV-E{Delta}M-HM2e and rVSV-E{Delta}M-tM2e are efficacious and protective universal vaccines against influenza.

microbiology

Life on leaves : uncovering temporal dynamics in Arabidopsis' leaf microbiota

Leaves are primarily responsible for the plants photosynthetic activity. Thus, changes in the phyllosphere microbiota, which includes deleterious and beneficial microbes, can have far reaching effects on plant fitness and productivity. In this context, identifying the processes and microorganisms that drive the changes in the leaf microbiota over a plants lifetime is crucial. In this study we analyzed the temporal dynamics in the leaf microbiota of Arabidopsis thaliana, integrating both compositional changes and changes in microbe-microbe interactions via the study of microbial networks. Field-grown Arabidopsis were used to follow leaf bacterial, fungal and oomycete communities, throughout the plants growing season (extending from November to March), over three consecutive years. Our results revealed the existence of conserved time patterns, with microbial communities and networks going through a stabilization phase (decreasing diversity and variability) at the beginning of the plants growing season. Despite a high turnover in these communities, we identified 19 core taxa persisting in Arabidopsis leaves across time and plant generations. With the hypothesis these microbes could be playing key roles in the structuring of leaf microbial communities, we conducted a time-informed microbial network analysis which showed core taxa are not necessarily highly connected network hubs and hubs alternate with time. Our study shows that leaf microbial communities exhibit reproducible dynamics and patterns, suggesting it could be possible to predict and drive these microbial communities to desired states.

microbiology

Prunella vulgaris extract and suramin block SARS-coronavirus 2 virus Spike protein D614 and G614 variants mediated receptor association and virus entry in cell culture system

Until now, no approved effective vaccine and antiviral therapeutic are available for treatment or prevention of SARS-coronavirus 2 (SCoV-2) virus infection. In this study, we established a SCoV-2 Spike glycoprotein (SP), including a SP mutant D614G, pseudotyped HIV-1-based vector system and tested their ability to infect ACE2-expressing cells. This study revealed that a C-terminal 17 amino acid deletion in SCoV-2 SP significantly increases the incorporation of SP into the pseudotyped viruses and enhanced its infectivity, which may be helpful in the design of SCoV2-SP-based vaccine strategies. Moreover, based on this system, we have demonstrated that an aqueous extract from the Chinese herb Prunella vulgaris (CHPV) and a compound, suramin, displayed potent inhibitory effects on both wild type and mutant (G614) SCoV-2 SP pseudotyped virus (SCoV-2-SP-PVs)-mediated infection. The 50% inhibitory concentration (IC50) for CHPV and suramin on SCoV-2-SP-PVs are 30, and 40 g/ml, respectively. To define the mechanisms of their actions, we demonstrated that both CHPV and suramin are able to directly interrupt SCoV-2-SP binding to its receptor ACE2 and block the viral entry step. Importantly, our results also showed that CHPV or suramin can efficiently reduce levels of cytopathic effect caused by SARS-CoV-2 virus (hCoV-19/Canada/ON-VIDO-01/2020) infection in Vero cells. Furthermore, our results demonstrated that the combination of CHPV/suramin with an anti-SARS-CoV-2 neutralizing antibody mediated more potent blocking effect against SCoV2-SP-PVs. Overall, this study provides evidence that CHPV and suramin has anti-SARS-CoV-2 activity and may be developed as a novel antiviral approach against SARS-CoV-2 infection.

microbiology