An Aedes-Anopheles Vaccine Candidate Supplemented with BCG Epitopes Against the Aedes and Anopheles Genera to Overcome Hypersensitivity to Mosquito Bites.

BACKGROUND: Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like fever. People with the syndrome develop serious allergies, ranging from rashes to anaphylaxis or shock. The few available studies on mosquito venom immunotherapy have utilized whole-body preparations and small sample sizes. Still, owing to their little success, vaccination remains a promising alternative as well as a permanent solution for infections like Skeeter's. METHODS: This study, therefore, illustrated the construction of an epitope-based vaccine candidate against Skeeter Syndrome using established immunoinformatic techniques. We selected three species of mosquitoes, Anopheles melas, Anopheles funestus, and Aedes aegypti, to derive salivary antigens usually found in mosquito bites. Our construct was also supplemented with bacterial epitopes known to elicit a strong TH1 response and suppress TH2 stimulation that is predicted to reduce hypersensitivity against the bites. RESULTS: A quality factor of 98.9496, instability index of 38.55, aliphatic index of 79.42, solubility of 0.934747, and GRAVY score of -0.02 indicated the structural (tertiary and secondary) stability, thermostability, solubility, and hydrophilicity of the construct, respectively. The designed Aedes-Anopheles vaccine (AAV) candidate was predicted to be flexible and less prone to deformability with an eigenvalue of 1.5911e-9 and perfected the human immune response against Skeeter (hypersensitivity) and many mosquito-associated diseases as we noted the production of 30,000 Th1 cells per mm3 with little (insignificant production of Th2 cells. The designed vaccine also revealed stable interactions with the pattern recognition receptors of the host. The TLR2/vaccine complex interacted with a free energy of - 1069.2 kcal/mol with 26 interactions, whereas the NLRP3/vaccine complex interacted with a free energy of - 1081.2 kcal/mol with 16 molecular interactions. CONCLUSION: Although being a pure in-silico study, the in-depth analysis performed herein speaks volumes of the potency of the designed vaccine candidate predicting that the proposition can withstand rigorous in-vitro and in-vivo clinical trials and may proceed to become the first preventative immunotherapy against mosquito bite allergy.

Designing a novel chimeric multi-epitope vaccine subunit against Staphylococcus argenteus through artificial intelligence approach integrating pan-genome analysis, in vitro identification, and immunogenicity profiling.

Staphylococcus argenteus is a newly identified pathogen that causes respiratory tract infections, skin infections, such as cellulitis, abscesses, and impetigo, and currently, there is no licensed vaccine available against it. To develop a vaccine against S. argenteus, a bacterial pan-genome analysis was applied to identify potential vaccine candidates. A total of 4908 core proteins were retrieved and utilized for identifying four proteins, including SG38 Panton-Valentine leukocidin LukS-PV protein, SG62 staphylococcal enterotoxin type A protein, SG39 enterotoxin B protein, and SG43 enterotoxin type C3 protein as potential vaccine candidates. Epitopes were predicted for these proteins using different types of B and T-cell epitope prediction tools, and only those with a non-toxic profile, antigenic, non-allergenic, and immunogenic were selected. The selected epitopes were linked to each other to form a multi-epitope vaccine construct, which was further linked to the PADRE sequence (AKFVAAWTLKAAA) and 50s ribosomal L7/L12 protein to enhance the vaccine's antigenicity. The three-dimensional structure of the vaccine construct was assessed to determine its binding affinity with key Toll-like receptor 9 (TLR-9) and Toll-like receptor 5 (TLR-5) immune cell receptors. Our findings demonstrate that the vaccine exhibits favorable binding interactions with these immune cell receptors, indicating its potential efficacy. Molecular dynamic simulations further confirmed the accessibility of vaccine epitopes to the host immune system, substantiating its ability to elicit protective immune responses. Taken together, this study highlights the promising candidacy of the modeled vaccine construct for future in vivo and in vitro experimental investigations.Communicated by Ramaswamy H. Sarma.

Chain-Engineering-Based De Novo Drug Design against MPXVgp169 Virulent Protein of Monkeypox Virus: A Molecular Modification Approach.

The unexpected appearance of the monkeypox virus and the extensive geographic dispersal of cases have prompted researchers to concentrate on potential therapeutic approaches. In addition to its vaccine build techniques, there should be some multiple integrated antiviral active compounds because of the MPV (monkeypox virus) outbreak in 2022. This study offers a computational engineering-based de novo drug discovery mediated by random antiviral active compounds that were screened against the virulent protein MPXVgp169, as one of the key players directing the pathogenesis of the virus. The screening of these candidates was supported by the use of 72 antiviral active compounds. The top candidate with the lowest binding affinity was selected for the engineering of chains or atoms. Literature assisted to identify toxic chains or atoms that were impeding the stability and effectiveness of antiviral compounds to modify them for enhanced efficacy. With a binding affinity of -9.4 Kcal/mol after chain, the lipophilicity of 0.41, the water solubility of 2.51 as soluble, and synthetic accessibility of 6.6, chain-engineered dolutegravir was one of the best active compounds, as proved by the computational engineering analysis. This study will revolutionize the era of drug engineering as a potential therapeutic strategy for monkeypox infection.

Full Ground Ultra-Wideband Wearable Textile Antenna for Breast Cancer and Wireless Body Area Network Applications.

Wireless body area network (WBAN) applications have broad utility in monitoring patient health and transmitting the data wirelessly. WBAN can greatly benefit from wearable antennas. Wearable antennas provide comfort and continuity of the monitoring of the patient. Therefore, they must be comfortable, flexible, and operate without excessive degradation near the body. Most wearable antennas use a truncated ground, which increases specific absorption rate (SAR) undesirably. A full ground ultra-wideband (UWB) antenna is proposed and utilized here to attain a broad bandwidth while keeping SAR in the acceptable range based on both 1 g and 10 g standards. It is designed on a denim substrate with a dielectric constant of 1.4 and thickness of 0.7 mm alongside the ShieldIt conductive textile. The antenna is fed using a ground coplanar waveguide (GCPW) through a substrate-integrated waveguide (SIW) transition. This transition creates a perfect match while reducing SAR. In addition, the proposed antenna has a bandwidth (BW) of 7-28 GHz, maximum directive gain of 10.5 dBi and maximum radiation efficiency of 96%, with small dimensions of 60 × 50 × 0.7 mm3. The good antenna's performance while it is placed on the breast shows that it is a good candidate for both breast cancer imaging and WBAN.