COVID-19 Therapeutics

COVID-19 Research Area(s): Vaccines & Treatments

A vaccine or therapeutic to protect against (or treat) infection by the coronavirus known as SARS-CoV-2, is urgently needed. Recent animal studies have shown that lipid nanoparticle (LNP) formulations of messenger RNA (mRNA) coding for proteins contained in a target virus can be used as vaccines. This technology was developed at UBC, in the Cullis group, and a similar approach is currently being clinically evaluated in the US.

In this approach, the body generates a robust immune response against what it believes to be an infectious agent. The benefit of such a technology is that it can be used to rapidly generate a novel vaccine (even to counteract mutations in the virus). Another research arm is the development of a therapeutic to neutralize the virus within the lungs - to help decrease viral load in patients already infected with the virus. We use an established concept of using the liver as a bioreactor to produce an antibody that is able to neutralise the virus within the lungs.The team assembled to conduct this project is drawn from the NanoMedicines Innovation Network (NMIN), a Canadian Networks of Centres of Excellence in nanomedicines, industry, and internationally recognised experts in drug delivery.

The current coronavirus pandemic is threatening the globe and efficient therapeutics to cure and prevent the viral infection are urgently needed. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An increasingly important application of nanomedicines, particularly lipid nanoparticle (LNP) formulations of mRNA, is to construct therapeutics and vaccines to elicit potent immunity against infectious diseases. The process for the development of LNP-mRNA systems as therapeutics or vaccines is conceptually straightforward and potentially very rapid. Briefly, the process involves (i) selecting SARS-CoV-2 neutralising antibody (therapeutic) or membrane proteins in the target virus that are likely to be antigenic (vaccine), (ii) making nucleoside-modified mRNA coding for these proteins, (iii) encapsulating these mRNAs in a LNP system, and (iv) administering the LNP-mRNA via intravenous (therapeutic) or intramuscular (vaccine) route. In case of a therapeutic approach the liver is used as a bioreactor for the production of the SARS-CoV-2 neutralising antibody. Facilitating the delivery of mRNA encoding membrane proteins to antigen-presenting cells results in a robust immune response.

All these steps can potentially be accomplished in a timeframe that is on the order of two or three months. The immune responses achieved are substantial and highly protective, as demonstrated in several recent studies by investigators of this research project for Zika virus, HIV, or influenza virus. The potential clinical viability of the LNP-based therapies is enhanced by the fact that the LNP components and methods of manufacture are similar to those employed for the clinically validated Onpattro® platform.