Frontrunners in the Race for a Coronavirus Vaccine

Two early candidates for vaccines to protect against Covid-19 are already undergoing animal trials on ferrets at the Australian Centre for Disease Preparedness, a high security laboratory in Geelong, Victoria. They both employ innovative approaches that depend only on knowing the genetic code of the novel corona virus (SARS-CoV-2), and this was published by Chinese scientists in early January. The fact they didn’t need quantities of the actual virus gave them a head start.  These two candidates were chosen by the Coalition for Epidemic Preparedness Innovations (CEPI), who are funding the Australian work and had already set up the pipeline before the covid-19 outbreak  began. The two teams leading the charge are:

The Oxford University Vaccine Group and Oxford's Jenner Institute are using a harmless non-replicating chimpanzee adenovirus to carry the genetic code for a protein found on the surface of the coronavirus (see picture).

Immune responses from other coronavirus studies suggest that these club-shaped spikes are a good target for a vaccine. After vaccination, the adenovirus enters our cells and starts to produce the surface-spike protein of the coronavirus, which then primes our immune systems to attack the coronavirus if it later infects our bodies. (Chimpanzee adenoviral vectors are a very well-studied vaccine type and have been used safely on thousands of subjects, from new-born babies to 90-year-olds, in vaccines targeting over 10 different diseases.)

Inovio is an American bio-technology firm specialising in DNA-based immunotherapy. The human cell has many amazing functions and in particular is a protein factory for making and maintaining our body parts. Their vaccine magically inserts a piece of the coronavirus DNA directly into the human cells in such a way that it can borrow the cell’s machinery to make the viral protein that will prepare the immune system to destroy any invasion by the actual virus before it can take hold. This is a completely novel approach and has not be used in a vaccine before.

Why Ferrets? In 2003, when a different coronavirus (SARS) struck, a team at the Scripps Research Institute in Florida discovered that it was getting into human cells by targeting a specific receptor called ACE2 on certain cells in the lining of the lungs and in other vital organs. It turns out these receptors in ferrets’ lungs are very similar to those in humans and make the ferret an ideal ‘guinea-pig’ to study the progression of covid-19 and the effectiveness of the vaccine. The first cohorts of ferrets were infected and separately inoculated in March and preliminary results should be available by the end of April. Another group of ferrets will receive a second booster dose of the vaccine before being infected. A full assessment of the trials will be made available to the two teams in the UK and the USA by mid-July. Meanwhile, both teams have started the first phase of clinical trials on humans.

Clinical trials. These typically have three phases:

Phase 1. A small group (around 40--50)  of brave people are shielded from exposure to the virus and injected with the vaccine to see if it has harmful effects. This is a safety test, not a test of efficacy. 

Phase 2. A much larger group of people from the general population who would be naturally exposed to the virus are divided into two groups. One half are injected with the vaccine, the other half with water; neither those carrying out the trial nor those participating know which group they belong to (a so-called double-blind trial). After a sufficient time elapses for exposure to have occurred, the levels of infection from the two groups are compared. Ideally the trials should be continued for a much longer time to find out how long immunity, if any, is conferred by the vaccine.

Phase 3. When the safety and the efficacy has been confirmed, the programme of large scale vaccinations is rolled out.

This project is a striking example of the power of international cooperation. If Inovio is successful, it could even go a small way to making America Great again!

Updates

1. CEPI receives its funding from philanthropic (e.g.Gates Foundation), institutional (e.g. Wellcome Trust) and international sources (Japan, Norway, Germany, Australia, Belgium and Canada). In March 2020, the British government pledged £210m. specifically to focus on a SARS-CoV-2 vaccine, making Britain CEPI's largest individual donor.

2. Ferrets now have a rival species for testing. When a Hong Kong team recently infected 8 hamsters with SARS-CoV-2, high levels of the virus were found in the hamsters’ lungs and intestines, tissues studded with the virus’ target  protein: angiotensin-converting enzyme 2 (ACE2). 

3. Two of the world's largest vaccine manufacturers, GlaxoSmithKline and Sanofi, are joining forces to develop a new vaccine to prevent Covid-19.