Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.

Characteristics and immunobiology of COVID-19

COVID-19 (coronavirus disease-2019) has been identified as a serious respiratory infection by the SARS-CoV2 virus (severe acute respiratory syndrome coronavirus 2), was first reported in Wuhan, Hubei Province, China in December 2019. World Health Organization (WHO) declared COVID 19 as a pandemic on March 11, 2020 considering the exponential spread and unmanageable mortality. It continues currently as the utmost urgent/critical ailment of global public health. Moreover, the COVID-19 pandemic has not only affected global health scenarios but also has heavily burdened the economic, financial, political, educational, and other dimensions of humanity across the world. Monitoring the COVID 19 pathology reveals a potential respiratory infection followed by severe pneumonia like clinical observations with greater chances of microvascular injuries and multiorgan failures in worse scenario. The preexisting comorbidities including type II diabetes, cardiovascular diseases, hypertension, and older age are other major aggravating factors. Rather than other flu viruses, the intricate interplay of SARS-CoV2 virus with the immune system underlies the pathological manifestations in both symptomatic and asymptomatic patients. This chapter highlights the role of heterogenous immune cell population, cytokine storm, immune cell activation, and potential signaling pathways associated with COVID 19 infection that are greatly appreciated to evolve novel translational therapeutic interventions. © 2022 Elsevier Inc. All rights reserved.