ABSTRACT
Introduction: The COVID-19 pandemic has been a major public health concern throughout the world. Various ventures of vaccine candidates are being studied rigorously in this regard and one such candidate is the receptor binding domain (RBD) of spike protein which interacts with angiotensin converting enzyme 2 (ACE2) on the host cell's membrane. Exploiting this interaction, many scientists across the world attempted to develop mRNA vaccine against SARSCoV- 2. A major lacuna associated with mRNA vaccines is their delivery through a suitable carrier, especially given the stability issues associated with mRNA vaccines. Aims & Objectives: The aim of our research is to develop an efficient mode of delivery of the self-amplifying mRNA (saRNA) against COVID 19. We have developed small vesicles from erythrocyte ghosts, known as nanoerythrosomes, which are in the nanometre range and focussed on development of nanoerythrosomes for delivery of mRNA-based vaccines. Material(s) and Method(s): Nanoerythrosomes were prepared from erythrocytes using osmotic and ultrasonic frequency stress and loaded with saRNA vaccine candidate. Thereafter, the nanoerythrosomes were characterized using Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) to confirm their homogeneity, integrity and size. The mRNA loaded nanoerythrosomes were used to deliver the mRNA in Vero E6 cells to evaluate its uptake. Result(s): The characterization of nanoerythrosomes using DLS and TEM revealed their size in the range of 100-200 nm. The delivery mediated by nanoerythrosomes was comparable to the Lipofectamine mediated uptake of saRNA indicating the excellent delivery efficacy of nanoerythrosomes. The added advantage of nanoerythrosomes mediated delivery is that they are rapidly taken up from blood by macrophages of the reticuloendothelial system (RES) that is present in liver, lung, and spleen. Thus the combination of saRNA and nanoerythrosomes can accelerate the uptake and antigen presentation in reticuloendothelial system and will provide an outstanding platform for the development of SARS-CoV2 vaccine. Conclusion(s): We developed a new approach to deliver mRNA vaccine candidates using nanoerythrosomes and successfully demonstrate its efficacy in vitro. This strategy can be further extended for the delivery of other vaccine candidates. (Figure Presented).
ABSTRACT
This paper study suggests the specifications for high-efficiency, short-haul utility aircraft. This class of aircraft is used extensively in the multinational express package delivery service. Concurrent with the COVID 19 pandemic upending passenger travel, there has been a broad increase in the demand for air cargo. We forecast a need for more efficient short and medium range aircraft that offer route time savings and lower operating costs. Using current market planes designed with similar mission requirements, payloads, and engines – a general plane was created and optimized around the operating model of the present-day FedEx package delivery feeder fleet. The modification and optimization process was completed using a Model-Based-Systems-Engineering (MBSE) approach utilizing Phoenix Integration’s ModelCenter, Excel, MATLAB, and SOLIDWORKS. The final design achieved 40% improvement in fuel efficiency over the current fleet, and improvements in speed, payload, and range while in compliance with FAA regulations as a class E cargo aircraft certified under 14 CFR Part 25. © 2022, American Institute of Aeronautics and Astronautics Inc, AIAA. All rights reserved.