There are dozens of vaccines, antiretrovirals and new supportive therapies being feverishly tested against COVID-19, and researchers say new technologies are enabling them to move faster than ever before.

COVID-19, a member of the coronavirus family that started popping up in January in China as a mystery pneumonia-like illness, closed the world’s manufacturing powerhouse for a time, has shut down Italy, and is rapidly spreading around the world.

Some, such as RBC Capital Markets’ chief US economist Tom Porcelli, are predicting a peak in new infections by April, if the virus behaves similarly to SARS.

A vaccine however is months away.

But new technologies, more funding, and past experience with SARS, MERS, H1N1 and Swine flu all suggest vaccine development this time could be quicker.

Israeli researchers reckon they could have a vaccine in just 90 days. The University of Queensland in January said it could have a vaccine on the market within six months using a new technology. German biotech Curevac says 12 months and US-based Inoiva Pharmaceuticals expects to have 1 million doses available by the end of the year.

 

Commercialising an emergency vaccine

Vaccines are not money makers for companies.

There haven’t been any known SARS outbreaks since 2004, Porcelli says, and there’s still no Zika virus vaccine following the outbreak in 2015/16.

Furthermore, the Ebola outbreak in 2014 showed how low-priority diseases affecting low-income populations are — various iterations of a vaccine had been shelved before the outbreak and it took five years after for a vaccine to be finalised and approved.

As such, organisations like the Coalition for Epidemic Preparedness Innovations (CEPI), launched in 2017 to make grants for swift vaccine development, and GAVI the Vaccine Alliance — founded by the Bill and Melinda Gates Foundation — are primary sponsors of vaccine development, particularly in emergencies such as COVID-19.

Brandon Capital Partners managing director Dr Chris Nave says vaccines are costly to develop and costly to maintain, if a disease is like the flu and constantly mutating.

“The industry takes these sorts of things very seriously,” he said.

“They will all be looking at what they have in their cupboard to try and see what they can develop for the community.”

Incentives such as minimum annual government purchases help.

Australia’s flu vaccine maker  CSL (ASX:CSL) has already said it’s not going it alone for COVID-19, as the illness is not similar to flu, but is providing support to the UQ researchers.

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Investing for an epidemic

Nave, who is also CEO of the Medical Research Commercialisation Fund, is more enthusiastic about antiretrovirals, which offer more immediate promise than lengthy vaccine development.

He says antiretroviral drugs, such as those already used for HIV and Hepatitis C, stop a virus’ ability to replicate once a person has been infected. It then lowers the severity of the disease and lowers the chance of it being passed on.

“That’s a really good exciting way for frontline development to try and stop the spread of the disease.”

US pharmaceutical company Gilead has started two randomised, open-label phase three trials into antiviral remdesivir, with results expected in May. Remdesivir was developed with Ebola and Marburg infections in mind, but has been proved effective against a range of viruses, including some in the coronavirus family.

Biotron (ASX:BIT), which has in the past tried to make antiretroviral vaccines against Hepatitis C and HIV, says it is looking in its portfolio for candidates that could be useful against COVID-19.

 

How vaccines work

“The main role of a vaccine is to present what’s called an antigen to your immune system that is a representation of a virus,” Nave says. “Vaccines train the immune system to recognise that virus”.

There are a variety of ways to make vaccines.

Live attenuated vaccines are a weaker form of the virus or bacteria, used for measles and the flu.

Inactivated vaccines are dead cells that still allow the body to learn how to fight live versions of diseases such as polio and rabies.

Subunit/conjugate vaccines are those where a protein or carbohydrate from the pathogen has been isolated and is the immune system’s target. It is used for conditions such as Hepatitis B, Human Papillomavirus (HPV), and Meningococcal.

Toxoid vaccines are used for bacterial infections in cases where the bacteria works by giving off dangerous, tissue damaging toxins. The bacteria is ‘deactivated’ in a mixture of formaldehyde and water. Diphtheria and Tetanus are two toxoid vaccines.

Conjugate vaccines link antigens from another pathogen to the outside of those, like Hib disease, which can hide from young immune systems. The body learns to recognise the sugary camouflage rather than the bacteria as harmful.

DNA and RNA vaccines are highly experimental and are simply a solution of the pathogen DNA, which teaches the immune system to produce antigens by itself. Herpes and flu DNA vaccines are under development.

Recombinant vector vaccines are also experimental and similar to a DNA vaccine. The difference is the DNA is a weakened version, allowing scientists to take a harmless pathogen, dress it in the DNA of a more dangerous disease, and train the body to recognise and fight both. Vaccines under development in this area include HIV and measles.

GAVI says using ‘platforms’ from existing diseases is speeding development up, and DNA-based vaccines could make the whole process significantly cheaper as all that is needed is a virus genome.

 

Who’s making COVID-19 vaccines

The WHO counted 35 separate vaccine initiatives on March 4. Among the more promising ones are:

1. The University of Queensland, with funding from CEPI, is using its “molecular clamp” technology to make a vaccine. The patented tech changes the shape of a specific protein on the virus allowing the immune system to recognise and kill it.

The technology can be applied to a range of animal and human viruses, says UQ professor Paul Young. GSK is providing the adjuvants, the ingredients that ‘aggravate’ the immune system enough to recognise the vaccine is present, and a Chinese biotech called Clover Biopharmaceuticals.

UQ was not able to provide an update on when it believes it will have a vaccine finished.

2. US-based, CEPI-funded Moderna Therapeutics shipped its first batch of vaccine for testing in late February, just 42 days after the virus was genetically sequenced.

A three-month phase one human trial in health patients is due to start in April, and a phase two trial in sick patients will launch after that.

Moderna’s treatment, developed with the US National Institute of Allergy and Infectious Diseases, is an mRNA (messenger ribonucleic acid) vaccine which introduces snippets of viral genetic code into a person so their own body produces the viral protein itself, thus alerting the immune system.

If it passes safety and efficacy testing, it would be the first mRNA vaccine allowed to be used in humans.

3. CureVac, another CEPI grantee, is also working on an mRNA vaccine.

CEO Daniel Menichella said in a press release that CureVac has already tested a rabies mRNA vaccine in humans and it believes it can get a vaccine candidate developed within a few months, even though they’re still in preclinical phases.

4. Vaccine specialist Novavax has received CEPI backing for a vaccine made from its recombinant protein nanoparticle technology.

The company expects to have a candidate for human trials by the end of May.

Like UQ, it is looking at the spike protein, the ‘key’ or hook that gains access to the cells the virus wants to invade, and plans to use its in-house adjuvant to boost immune responses. It has already made vaccines against SARS and MERS.

5. Oxford University has been funded to see if it can produce an effective vaccine, a “replication-deficient simian adenoviral vaccine vector” or a vaccine containing a virus that causes common colds in apes and can no longer reproduce.

Its ChAdOx1 candidate is a safe version of an adenovirus, which can cause a common cold-like illness.

It’s been modified so it cannot reproduce and enhanced with COVID-19 genetic code to provide instructions for making the coronavirus spike protein.

The university has so far used the platform to develop vaccines against Lassa, Nipah, and MERS, with the latter completing phase one studies.

6. Inovio Pharmaceuticals already has a promising MERS vaccine in human trials. Recently the biotech and its partner Beijing Advaccine Biotechnology won a CEPI grant for a COVID-19 vaccine.

Inovio’s vaccine is a DNA approach, and the company plans to have it in human trials later this year.

7. Johnson & Johnson’s Janssen, alongside the US Biomedical Advanced Research and Development Authority (BARDA), is exploring a more traditional vector-based vaccine, using a non-replicating virus that has been injected with some COVID-19 genetics. It plans to start human trials from September.

8. And vaccine grandfather Sanofi Pasteur, also working with BARDA, is following its flu vaccine formula and making a version of the viral protein. Human trials could start within the year.