Using RNA Vaccines to tackle emerging disease threats

Posted on 2021-02-26

Vaccination has greatly reduced the incidence of infectious diseases, and has revolutionised modern medicine. However, conventional vaccine approaches are not as effective against rapidly evolving pathogens and emerging disease threats.

RNA based vaccines could prove effective in these areas, with decreased manufacturing times and greater effectiveness. They are also seen as potential novel therapeutic option for major diseases like cancer.

• Faster and cheaper to produce
• Safer for the patient, as they are not produced using infectious elements (not made with pathogen particles or inactivated pathogen)
• Production is laboratory based: the process can therefore be standardised and scaled, improving responsiveness to emerging outbreaks
• Therefore, shows promise in providing a quick response to large outbreaks and epidemics 
• Current research into RNA vaccines is for infectious diseases and cancer; using RNA vaccines to treat allergy is still at the early research stage
• Early clinical trial results suggest the vaccines generate a reliable immune response and have few side effects in healthy individuals

Conventional vaccines

Usually contain inactivated disease-causing organisms/proteins, which mimic the infectious agent. This stimulates the body’s immune response. 

RNA vaccines

Consist of an mRNA strand (this molecule tells cells what to build) which is coded for a disease-specific antigen. Once inside the cell, the cells use the genetic information to produce the antigen. This is displayed on the cell surface and recognised by the immune system in the body, preparing it to fight the real thing. 

Non-replicating mRNA

An mRNA strand is packaged and delivered to the body. This is taken up by the body’s cells to make the antigen.

In vivo self-replicating mRNA

A pathogen-mRNA strand is packaged with additional RNA strands; this ensures it will be copied when the vaccine is inside the cell. This helps to ensure a more robust immune response.

In vitro dendritic cell non-replicating mRNA vaccine

Dendritic cells are versatile controllers of the immune system, responsible for the initiation of adaptive immune responses. They present antigens on their cell surface to other types of immune cells, stimulating an immune response. The cells are extracted from the patient’s blood, transfected with the RNA vaccine, and given back to the patient

Can be produced in the laboratory from a DNA template using readily available materials. This is less expensive and faster than conventional vaccine production.

There are a number of available methods for delivering the vaccine:

• Via needle-syringe injections/needle-free into the skin
• Via injection into the blood, muscle, lymph node
• Directly into the organs
• Via a nasal spray

The optimal delivery technique is not yet known. 

• The mRNA strand in the vaccine may elicit an unintended immune reaction (this is minimised by designing the mRNA vaccine sequences to mimic those produced by mammalian cells)
• Delivering the vaccine effectively is challenging as the RNA, once free in the body, is quickly broken down (the effects of this are minimised by incorporating the RNA strand into a larger molecule to help stabilise it)
• Many RNA vaccines need to be frozen/refrigerated. Work is ongoing to produce vaccines that can be stored outside the cold chain, for use in countries with limited facilities
• Clinical trial data is limited, and it is not yet certain which production method(s) are the best, production is also currently small-scale and it is not clear if current methods are scalable

Whilst these are not yet considered standard treatment, the COVID-19 vaccine is an RNA and currently in use.

Research Articles:

RNA vaccines: an introduction

An mRNA Vaccine against SARS-CoV-2 - Preliminary Report

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine