An interesting article in the Scientific American published in July this year suggests that now scientists have learned how to create artificial proteins, this leads to the development of new COVID vaccines which could revolutionise biology.

Lexi Walls, a researcher from the University of Washington is an expert on coronaviruses.  She has spent many months researching a new kind of vaccine against coronavirus.  She hoped that her approach, if successful, would not only stem COVID but also revolutionise the field of vaccinology – hopefully helping to defeat infectious diseases such as influenza and HIV.

Unlike any vaccine used before, the vaccine Walls was developing is not derived from components found in nature.  It consists of artificial microscopic proteins drawn up on a computer, and their creation marks the beginning of the extraordinary leap in the human’s ability to redesign biology.

Proteins are intricate nanomachines that perform most tasks in living things by constantly interacting with one another.  They digest food, fight invaders, repair damage, sense their surroundings, carry signals, exert force, help create thoughts and replicate. 

They are made of long strings of simpler molecules called amino acids and they twist and fold into enormously complex 3D structures.

Their shapes are governed by the order and number of the different amino acids used to build them, which have distinct attractive and repellent forces.  The complexity of those interactions is so great and the scale so small, the average cell contains 42 million proteins, that we have never been able to figure out the rules governing how they spontaneously and dependently contort from strings to things and many experts have assumed that we never would. 

New insights and breakthroughs in artificial intelligence are coaxing, or forcing, proteins to give up their secrets.  Scientists are now forging biochemical tools that could transform our world.  With these tools, proteins can be used to build nanobots that can engage infectious diseases in single particle combat, or send signals throughout the body, or dismantle toxic molecules like tiny repo units, or harvest lights.  Biology can be created with a purpose.  

Lexi Walls is at the forefront of this research.  She completed a doctorate in Coronavirus structure in December 2019. 

She predicted a pandemic and unfortunately, that ended up coming through.  She knew that when this mysterious pneumonia trickled out of Wuhan China in late December 2019 that it was going to be a Coronavirus.  When the genetic sequence for SARS-CoV-2 was released to the world on January 10, 2020 Walls and her biochemist David Veesler, the head of her lab at the University of Washington, stayed up all night analysing it.

Like other coronaviruses SARS-CoV-2 resembles a ball covered in protein spikes.  Each spike ends in a cluster of amino acids – a section of the protein known as the receptor binding domain, or RBD – whose alignment and atomic charges pair perfectly with a protein on the surface of the human cells.  The viral protein docks at the receptor like a spacecraft, and the virus uses this connection to slip inside the cell and replicate. 

Because of its dangerous role, the RBD is the primary target of immune systems’ antibodies.  They too are proteins created by the body to bind to the RBD and take it out of commission, but it takes a while for specialised cells to manufacture enough effective antibodies, and by that time the virus has often done its considerable damage. 

The first generation COVID vaccines, including the mRNA vaccine that has been such lifesavers, work by introducing the viruses spike into the body, without a functional Coronavirus attached, so the immune system can learn to recognise the RBD and rally its troops, but the RBD is periodically hidden by other parts of the spike protein, shielding the domain from antibodies looking to bind to it.  This blunts the immune response.  In addition, a free floating spike protein does not resemble the natural virus and does not always trigger a strong reaction unless a large dose of vaccine is useful.  This big dose increases the costs and can trigger strong side effects.  

As successful as the COVID vaccines have been, many experts see inoculations based on natural proteins as an interim technology. 

Walls and Veesler had an idea – what if, instead of a whole spike, the immune system was presented with just the RBD tip, which would not have any shield to hide behind.  The initial issue with this idea was that biology does not make isolated RBDs and the segment on its own would be too small and unfamiliar to get the immune system’s attention.  However, Walls and Veesler approached the Bell Labs of protein invention at the University of Washington’s Institute for protein design and asked them to try a similar nanoparticle core for SARS-CoV-2 vaccine as they had done to the respiratory syncytial virus.  This protein based nanoparticle would be cheap and fast to produce, it would be stable at room temperature and easy to deliver to people unlike fragile mRNA vaccines that need to be kept in the deep freeze. 

They fused the RBDs directly to the surface of the nanoparticle and then tethered them with a short string of amino acids like kites.  This gave the RBDs a little bit of play, which would allow the immune system to get a better look at every angle and produce antibodies that could attack many different spots.  Further studies showed that this combination, the nanoparticle vaccine caused a reaction where antibodies were smothering it and it had 10 times the neutralising effect of large dose spike preparations.  These nanoparticles entered the last testing phase early in 2021 and this new technology, which had proven to be already a success, had arrived. 

The London General Practice the leading London Doctor’s clinic applauds the government on its vaccination programme and encourages all those who are eligible to be vaccinated.

Dr Paul Ettlinger
Founder, The London General Practice

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