Vector Signals

De: Maddy Chang McDonough
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  • A private, AI-curated podcast delivering 15-20 minute deep dives into the latest Nature articles on mosquito-borne viruses and AI-driven therapeutic breakthroughs. Designed for the researchers of the Saleh Lab at Institut Pasteur, each episode distills cutting-edge science into accessible insights—so you can stay current, even during your busiest bench days.
    © 2025 Maddy Chang McDonough
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  • Blocking Malaria Transmission with PfPIMMS43 Nanobodies (April 2025)

    Blocking Malaria Transmission with PfPIMMS43 Nanobodies (April 2025)
    May 3 2025
    Briefing Document: Nanobody-Mediated Blocking of Malaria Transmission Targeting PfPIMMS43Source: Excerpts from "s42003-025-08033-8.pdf" (A Nature Portfolio journal; https://doi.org/10.1038/s42003-025-08033-8) Authors: Chiamaka Valerie Ukegbu, et al. Date: Received - 04 December 2024 | Accepted - 02 April 2025 | Published - 30 April 2025Executive Summary:This study explores a novel strategy to block malaria transmission by targeting the Plasmodium falciparum protein PfPIMMS43 using single-domain VHH antibodies, also known as nanobodies. PfPIMMS43 is a critical surface protein for the parasite's development within the mosquito, specifically during the transition from ookinete to oocyst, and aids in evading the mosquito's immune response. Building on previous research demonstrating the potential of polyclonal antibodies against PfPIMMS43, this study successfully developed and characterized high-affinity nanobodies derived from llamas. These nanobodies were shown to significantly reduce both the intensity and prevalence of P. falciparum infection in Anopheles mosquitoes using both laboratory and field strains of the parasite. The study mapped the binding epitopes of the nanobodies to conserved regions in the second half of PfPIMMS43, confirming epitope accessibility. These findings establish PfPIMMS43 as a promising target for malaria transmission-blocking interventions and propose an innovative strategy utilizing genetically modified mosquitoes expressing these nanobodies in conjunction with gene drive technology for enhanced malaria control and elimination efforts.Key Themes and Important Ideas:Malaria Transmission as a Target: The study emphasizes the importance of targeting the parasite's development within the mosquito vector to interrupt the human-to-mosquito and mosquito-to-human transmission cycle. This is presented as a crucial approach to complement existing malaria control measures, especially in the face of challenges like insecticide failure, climate change, and funding limitations. The transition from ookinete to oocyst in the mosquito midgut is identified as a "key developmental bottleneck" for the parasite.PfPIMMS43 as a Critical Transmission Target: The research highlights PfPIMMS43 as an "indispensable" surface protein for P. falciparum ookinetes and sporozoites. It is crucial for the ookinete-to-oocyst transition and plays a role in the parasite's ability to "evade the mosquito immune responses," specifically the complement-like system in the hemolymph. Previous studies, including those by the authors, had already indicated the potential of polyclonal antibodies targeting this protein in reducing transmission.Nanobodies as a Promising Intervention Tool: The study focuses on the development and application of VHH domain nanobodies as an alternative and potentially superior approach to conventional antibodies for transmission blocking. Nanobodies, derived from camelids and sharks, are described as "smaller, more easily produced monoclonal, heavy-chain variable (VHH) domain antibodies." Their advantages include:"small size (~15 kDa)""structural simplicity""strong binding affinity"Easily bioengineered for targeting parasite antigens in mosquito vectors.Development and Characterization of PfPIMMS43 Nanobodies: High-affinity nanobodies targeting PfPIMMS43 were successfully generated by immunizing llamas with recombinant PfPIMMS43. Nine nanobodies were selected based on variations in their antigen-binding regions (CDR1-3). Four nanobodies (G9, E5, C12, and E2) exhibited high nanomolar binding affinities to recombinant PfPIMMS43 (3, 5, 6, and 8 nM, respectively). These four nanobodies were also able to detect endogenous PfPIMMS43 protein expressed by P. falciparum ookinetes in infected mosquito midguts.Significant Transmission Blocking Activity (TRA): The developed nanobodies demonstrated significant transmission-reducing activity in mosquito feeding assays.In standard membrane feeding assays (SMFAs) using laboratory P. falciparum NF54 and An. coluzzii mosquitoes, the four high-affinity nanobodies (G9, E5, C12, and E2) significantly reduced oocyst numbers at a concentration of 100 µg/ml, with reductions ranging from 83% to 99%. Oocyst reduction was concentration-dependent.In direct membrane feeding assays (DMFAs) using natural P. falciparum isolates from gametocytaemic children in Tanzania and local An. gambiae mosquitoes, G9 and E5 (the two nanobodies with the highest affinities to recombinant PfPIMMS43) also showed significant TRA, with reductions of 99% and 79% at 100 µg/ml, respectively. Both nanobodies significantly reduced mosquito infection prevalence in field conditions.Epitope Mapping and Structural Insights: Epitope mapping revealed that the four nanobodies bind to "conserved regions in the second half of PfPIMMS43," specifically beyond amino acid residue 258. This suggests the C-terminal half of the protein is more immunogenic. G9 and E5 appear to recognize similar conformational ...
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    13 m
  • Nanofiber Encapsulation of Pseudomonas for Sustained Mosquito Larvicide Release (April 2025)

    Nanofiber Encapsulation of Pseudomonas for Sustained Mosquito Larvicide Release (April 2025)
    Apr 21 2025
    Briefing Document: Nanofiber Encapsulation of Pseudomonas aeruginosa for Sustained Mosquito Larvicide ReleaseDate: Received - 13 December 2024 | Accepted - 04 April 2025 | Published - 21 April 2025 Source: Excerpts from "Nanofiber encapsulation of Pseudomonas aeruginosa for the sustained release of mosquito larvicides" https://doi.org/10.1038/s41598-025-97400-w1. Executive Summary:This study investigates a novel approach for mosquito vector control using nanofiber encapsulation of the bacterium Pseudomonas aeruginosa. The research addresses the inadequacy of current vector control strategies in eliminating mosquito-borne diseases by developing a method for the sustained release of bacterial larvicides. P. aeruginosa was selected for its potent larvicide production compared to other tested Pseudomonas species. The study demonstrates that encapsulating P. aeruginosa in electrospun nanofibers protects the bacteria, mimicking natural biofilms, enhances their survival in aquatic environments, and allows for prolonged larvicide production without harming non-target organisms (guppy fish). This nanotechnology-based method shows promise for controlling mosquito larvae in various breeding habitats over extended periods, potentially reducing application frequency and costs.2. Background and Problem Statement:Mosquito-borne diseases (malaria, dengue, chikungunya, Zika, etc.) pose a significant global health threat, affecting hundreds of millions annually.Existing vector control strategies, primarily chemical insecticides and environmental management, are often insufficient for complete vector elimination.Increased insecticide resistance and environmental concerns associated with chemical methods necessitate the development of novel, sustainable approaches.Biological control using bacteria like Bacillus thuringiensis var. israelensis and Bacillus sphaericus offers a safer alternative, but their efficacy depends on persistence in the environment.Sustained-release formulations of microbial larvicides are highly desirable to reduce application frequency and costs.Conventional immobilization techniques for sustained release often suffer from limitations like low diffusion and reduced microbial viability."Despite the rising global incidence of vector-borne diseases such as malaria, dengue, chikungunya, and Zika, existing vector control strategies remain inadequate for completely eliminating vectors from their breeding sites."3. Key Findings and Concepts:Superiority of Pseudomonas aeruginosa: Among the tested Pseudomonas species (P. fluorescens and P. putida), P. aeruginosa demonstrated the most potent larvicidal activity against four major mosquito vectors: Aedes aegypti, Culex quinquefasciatus, Cx. tritaeniorhynchus, and Anopheles stephensi."During the initial screening, Pseudomonas aeruginosa proved to be more effective than the other two tested species, P. fluorescens and P. putida, in producing potent larvicides and was therefore selected for nanofiber encapsulation studies."Nanofiber Encapsulation Technique: Electrospinning was used to create a thin fibrous material at the nanoscale (1 nm - 1 µm) from Pluronic F127 dimethacrylate (F127-DM) and polyethylene oxide (PEO) to encapsulate and immobilize live P. aeruginosa bacteria."In the present study, we rectified the shortcomings of conventional immobilization by developing a thin fibrous material at the nanoscale level (typically between 1 nm and 1 µm) using electrospinning to encapsulate and immobilize live bacteria."Protection and Sustained Release: Nanofiber encapsulation shields the bacterial cells from environmental stress, mimicking natural biofilms, thereby enhancing their survival and prolonging larvicide production. The cross-linking of the nanofibers prevents their rapid dissolution in water."This study aimed to encapsulate larvicide-producing bacteria in nanofibers designed to shield bacterial cells from environmental stress—mimicking natural biofilms—thereby enhancing their survival in aquatic habitats and prolonging larvicide production."Efficacy in Batch Systems (Container Breeding Habitats): Nanofiber-encapsulated P. aeruginosa demonstrated sustained larvicidal activity in batch systems (simulating stagnant water bodies). The spent water containing released metabolites remained lethal to all four tested mosquito species for at least 8 days."In the batch system, the spent water with metabolites of P. aeruginosa was lethal to all the tested species of larvae, such as Ae. aegypti, An. stephensi, Cx. tritaeniorhynchus, and Cx. quinquefasciatus, to varying degrees... The larvicidal potency of the spent water either remained the same as observed on the first day or increased during the subsequent days of incubation."Reduced Efficacy in Continuous Systems (Flowing Water Habitats): In continuous flow systems (simulating paddy fields or tanks with water inflow), the larvicidal efficacy of the released metabolites declined over subsequent days, suggesting...
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    14 m
  • Predicting Aedes Albopictus Spread in Europe via Climate and Population (April 2025)

    Predicting Aedes Albopictus Spread in Europe via Climate and Population (April 2025)
    Apr 11 2025
    Population Dependent Diffusion Model for Aedes Albopictus Spread in EuropeSource: Barman et al., "A climate and population dependent diffusion model forecasts the spread of Aedes Albopictus mosquitoes in Europe," Nature Portfolio journal, 2025, https://doi.org/10.1038/s43247-025-02199-zDate: Received - 25 November 2024 | Accepted - 07 March 2025 | Published - 09 April 2025Key Themes and Important Ideas/Facts:This paper presents a novel spatio-temporal diffusion model that accurately forecasts the spread of Aedes albopictus mosquitoes in Europe by simultaneously considering climate suitability and human population factors. Ae. albopictus is a crucial vector for several arboviruses, including Dengue, Chikungunya, Zika, and Yellow Fever. The study highlights the increasing risk of autochthonous (local) transmission of these diseases in Europe due to the mosquito's expanding range, driven by environmental changes and global interconnectedness.1. Predictable Spread of Ae. albopictus:The core finding is that the expansion of Ae. albopictus in Europe is predictable by integrating climate suitability and human population predictors within a single spatio-temporal diffusion model.The model demonstrates high accuracy in predicting areas of presence and absence (99% and 79% respectively).This predictability allows for anticipating future outbreaks by understanding the interplay between vector suitability and introduction.Quote: "These results show that the expansion of Ae. albopictus in Europe is predictable and provide a basis for anticipating future outbreaks in situations of dependent interacting co-drivers."2. Drivers of Ae. albopictus Expansion:The study confirms that climate change (suitable climatic conditions), urbanization, and human population mobility are key factors facilitating the invasion of new habitats by this species.Quote: "Suitable climatic conditions favoured by climate change, urbanisation, and human populationmobility, seems to have facilitated the expansion of this invasive mosquito species into novel habitats."The passive transport of eggs through global travel and trade (e.g., used tires, lucky bamboo) and ground vehicles contributes significantly to its spread along transportation corridors.The mosquito's ecological and physiological plasticity (e.g., adaptation to cold, desiccation-resistant eggs, domestic container-breeding) enables its rapid and widespread expansion.3. Model Development and Performance:The researchers developed a "highly predictive spatio-temporal vector diffusion model" that integrates climate suitability (temperature, humidity) and human population data.The model is a generalized additive mixed (GAM) model fitted within a Bayesian framework (INLA).It accounts for both short-range spread (geographical proximity) and potential long-range spread influenced by human population.The model demonstrates good overall performance, with AUC values around 0.80 for predicting new establishments in previously uncolonized areas.Quote: "Notably, model evaluation reveals that new introduction of Ae. albopictus into naïve areas, are very well predicted, which has not been achieved before with this type of model."Two versions of the model were calibrated: one using raw climate and population covariates, and another using a mechanistic mosquito life cycle model output as a covariate. Both showed similar predictive performance.4. Key Covariates and Their Influence:Temperature: Median temperature (up to 24°C) shows a strong positive correlation with Ae. albopictus presence, decreasing at higher temperatures. Minimum temperature is positively correlated when median temperatures are high.Relative Humidity: Low relative humidity is negatively correlated with Ae. albopictus presence.Proximity: Geographical proximity to already established areas has a substantial impact on the spread, modeled through a spatio-temporal diffusion process.Human Population: Higher population density is associated with a higher likelihood of Ae. albopictus presence, likely reflecting increased introduction opportunities via human mobility, although the measured effect size was relatively small compared to climate factors.Human mobility modeled explicitly using a radiation model did not significantly improve model fit, suggesting that local diffusion and the human population covariate together can effectively capture its impact.5. Implications for Public Health:The model can be a valuable tool for preparedness and response to Aedes-borne infections by identifying high-risk areas for new introductions.Quote: "This model can be integrated into early warning systems and help delineate areas at risk for the introduction and establishment of Ae. albo-pictus."Predictions can help target awareness and prevention messages to susceptible populations and guide vector control efforts.The model can also inform healthcare system preparedness for potential epidemics and the strategic deployment of available arboviral vaccines...
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    13 m
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