Biology subjects

Angeles, J.

Publications and source records attributed to Angeles, J..

4 recordsLinked to original sources

bioRxiv2023

Insecticide resistance in Aedes aegypti from the National Capital Region, Philippines

BackgroundHuman arboviral diseases such as dengue, chikungunya and Zika can be transmitted by the mosquito Aedes aegypti. The insecticide-based vector control strategy is critical in reducing the transmission of these Aedes-borne diseases but is threatened mainly by the emergence of insecticide resistance. Methodology/Principal FindingsAdult Aedes aegypti from National Capital Region, Philippines were subjected to bioassay to determine their susceptibility to the diagnostic doses of pyrethroid, organochlorine and organophosphate insecticides following the standard World Health Organization insecticide susceptibility test. This study reports for the first time the existence of insecticide resistance in Ae. aegypti from the Philippines to pyrethroids and organochlorine. Results from this study showed that most of the Ae. aegypti populations exhibited phenotypic resistance to the pyrethroids (permethrin and etofenprox) and an organochlorine (DDT) while all populations tested to malathion were still susceptible to this organophosphate. Varying resistance levels to deltamethrin, cyfluthrin and lambdacyhalothrin were also observed in the different mosquito populations. ConclusionsInsecticide resistance exists in local populations of Ae. aegypti from the National Capital Region. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy. Best practices that are proven to prevent and/or delay the development of insecticide resistance such as insecticide rotation should be implemented. Alternative toxicants and chemicals with a different mode of action, such as repellents, should be explored to ensure continuing efficacy of program interventions. Author summaryThe National Capital Region (NCR), Philippines reports the countrys highest dengue incidence. Apart from being populous and the center of economic activity, the local government authorities of this region have undertaken significant vector control efforts devoted to dengue. The use of insecticides to reduce mosquito vector density remains the handiest control method. This scenario necessitated the documentation of the resistance levels, particularly of the most important vector Aedes aegypti. An insect is said to be resistant when the known effective dose of an insecticide can no longer sufficiently kills the same insect population. This study showed that Ae. aegypti population from cities in NCR had developed resistance to commonly used pyrethroids (permethrin, etofenprox) and to an organochlorine (DDT). Highly localized variations of resistance and susceptibility within cities at NCR were recorded against deltamethrin, cyfluthrin and lambdacyhalothrin. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy.

pharmacology and toxicology↗

bioRxiv2023

Multivalent Exosome based protein vaccine: a "mix and match" approach to epidemic viruses' challenges.

Endemic viruses are becoming increasingly the norm, and the development of a rapid and effective vaccine is emergent. Here, we used our StealthX exosome platform to express either Influenza H3 (Stealth X-Hemagglutinin, STX-H3) or SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-H3 and STX-S induced a strong immunization with the production of a potent humoral and cellular immune response in mice. Interestingly, these effects were obtained with administration of nanograms of protein and without adjuvant. Therefore, we tested the possibility of a multivalent vaccine: STX-H3 and STX-S exosomes were formulated together in a "mix and match" approach and the immune response was further evaluated. We showed that our STX-H3+S cocktail vaccine is as effective as the single components administered separately, resulting in a strong antibody and T-cell response. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.

immunology↗

bioRxiv2023

Nanograms of SARS-CoV-2 Spike Protein Delivered by Exosomes Induce Potent Neutralization of Both Delta and Omicron Variants.

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricors StealthX platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthX exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.

immunology↗

bioRxiv2023

Exosome based multivalent vaccine: achieving potent immunization, broaden reactivity and T cell response with nanograms of proteins without any adjuvant.

Current approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultra-low storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed which offer broader immunity but require significant time for development and use of an adjuvant to boost immune response. Here, exosomes were used to deliver a bi-valent protein-based vaccine, in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) or the more conserved nucleocapsid (Stealth X-Nucleocapsid, STX-N) protein on the surface. When administered as single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these results were obtained with administration of only nanograms of protein and without adjuvant. In two independent animal models (mouse and rabbit), administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike and strong T-cell responses. Importantly, no competition in immune response was observed, allowing for delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthXTM exosome platform has an enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low dose vaccine resulting in potent, broader immunity.

immunology↗