Covid-19

The scramble for vaccine frontrunners

Who has dibs on the first doses of Covid-19 vaccine and how quickly can phase three trials be run?

Hedging bets, the United Kingdom has pre-ordered five doses of Covid-19 vaccine for every person in the country.

None of these pre-ordered vaccines are approved for general use yet and some may never be. Politely it's been described as "vaccine nationalism". Others see it as hoarding.

It's not the only wealthy country guilty of hoarding vaccines. The United States has pre-ordered 800 million doses for its population of 330 million. Japan and the European Union have pre-ordered at least one dose of vaccine per person.

Forty percent of the estimated vaccine capacity to the end of 2021 has been pre-ordered according to an analysis published in Nature.

As the World Health Organisation (WHO) director Tedros Adhanom Ghebreyesus pointed out "vaccine nationalism" isn't going to help the global economy.

"If we don't protect these highest risk people from the virus everywhere and at the same time, we can't stabilise health systems and rebuild the global economy ... [a] vaccine developed in one country may need to be filled in vials with stoppers that are produced in another, using materials for the high-grade glass that is only available from yet another country.

WHO's favoured approach is a programme called Covax, which aims to ensure equitable distribution. Its plan is to vaccinate 20 percent of each member country who are at the highest risk, such as health workers, the elderly and those with underlying conditions. This is hoped to end the acute phase of the pandemic.

Put together by the Coalition for Epidemic Preparedness Innovations (CEPI), global vaccine alliance group Gavi, the programme funded a number of vaccine developers at the outset of the pandemic. Now it hopes that backing will pay off with supply commitments which were not necessarily in place as a condition of funding.

Covax's goal is to distribute two billion doses of vaccine in 2021. One billion doses for low to middle-income countries, to be supplied free or at low cost, and the rest for wealthier countries that will pay for their vaccines. It's buyers club on a huge scale. More countries signing up and contributing funds means less competition and, hopefully, better deals with the vaccine manufacturers.

So far around 172 countries are potentially part of the scheme and Covax has secured 330 million doses of the University of Oxford/AstraZeneca vaccine. Moderna, which received funds from the scheme, now has billions in commitments from the US, dwarfing the money it received from Covax. No deal has been struck with that company yet.

One of the largest players, the US, is refusing to join.

"We will not be constrained by multilateral organisations influenced by the corrupt World Health Organisation and China," said a White House spokesperson.

Russia and China have also not been confirmed as joining the programme.The Financial Times has reported the deadline for joining the programme has been extended from August 31 to September 18 as wealthy nations have been slow to join, seeking their own deals instead.

It's estimated around 70 percent of the world's population - 5.5 billion people - will need immunity to the virus to stop the pandemic.

Recent reports have confirmed reinfections have already occurred in some people. This handful of cases could be just in people who didn't generate much of an immune response to their first infection, but even with a strong immune response, eventual reinfection is thought to be a risk. This means the 25 million people who have already had the virus are likely to need vaccination at some point if the virus continues to circulate.

What's New Zealand doing?

New Zealand is pursuing three paths.

We've joined the Covax scheme. In an announcement late August it was said hundreds of millions of dollars had been put toward securing a vaccine. Exact figures weren't released as they could impact the ability to negotiate.

The second option is to manufacture someone else's vaccine under licence here. New Zealand biotech company BioCell has been funded $3 million. Research, Science and Innovation Minister Megan Woods said this would help the company produce up to 100 million doses which would be shared with Pacific countries.

The final option is to develop our own vaccine. A Vaccine Alliance Aotearoa New Zealand has been formed - Ohu Kaupare Huaketo - and $10 million of government funding has been put towards its work. It's made up of the Malaghan Institute of Medical Research, University of Otago and Victoria University of Wellington. These three institutions launched into action as soon as the pandemic started. 

“What we’re looking at is an international landscape where Covid-19 vaccines are being developed rapidly for an emergency response, while others - the second generation vaccines - are being designed with our increasing knowledge of immunity to SARS-CoV-2. These are ones, for example, that will provide lasting immunity, protect older and more vulnerable people, and can be scaled up and distributed easily and cheaply. At this stage, the more vaccines being researched and developed the better - it gives us choices," said Malaghan Institute director professor Graham Le Gros.

There's a recent wildcard to the three options. Former politicians Ross Meurant and Don Brash said they were aiming to purchase and import the Russian vaccine Sputnik V made by the Gamaleya Research Institute. It's been through phase one and two trials but data has not been published. It was then approved for use without a phase three trial. This has now been scaled back and a phase three trial is now planned. Before it can be used in New Zealand it would require Medsafe's approval.

How far away are vaccines?

The race for a vaccine is likely to have more than one winner. Hundreds of vaccines are being developed and there's an expectation by mid-to-late 2021 there will be vaccines available for general use. Some companies suggest they may be ready even earlier. 

There's a pipeline of testing that vaccines need to go through before they're licensed for use. The safety bar is set high and they're tested on thousands of people before they're approved by regulators. Some vaccines are now in the final phase of trials before approval.

More information on each of these frontrunners can be found further down the page.

There's a chance, if interim results from the final phase of trials look positive, some countries may consider allowing emergency use of a vaccine. Vaccine producers are hedging their bets, already manufacturing vaccines, so as soon as approval occurs, there will be doses to ship. 

How quickly can results from phase three trials be interpreted?

University of Auckland vaccinologist associate professor Helen Petousis-Harris says it comes down to where the phase three trials are taking place.

These trials are usually done with thousands of people. Half are given the vaccine and half a placebo. If the people given the vaccine don't get the virus and the people who got the placebo do get the virus, it's clear the vaccine has worked. It's considered unethical to intentionally infect thousands of people with a potentially fatal virus to get a result. Instead, the people are watched over time as they go about their normal lives. 

"If you don't have enough Covid around, or you don't go for long enough to accumulate enough cases or events, you're not going to have enough data to be able to draw conclusions."

At present trials are running in countries like Brazil, South Africa, Indonesia and the United Arab Emirates, where the virus is circulating. 

"If your trial is running in a hotbed of Covid, and you want to measure infections, you probably won't have to go for long before your study participants start to accumulate infections."

Petousis-Harris knows of one trial expected to gather results after four months.

National Institute for Allergy and Infectious Diseases director Anthony Fauci has said in a trial with 30,000 participants you would be need around 150 cases of Covid-19 to tell whether the vaccine was working. 

Regulatory approval is the next step. This is done on a country-by-country basis, involving hundreds of pages of information. In the US the agency is the Food and Drug Administration (FDA), in Europe it's the European Medicines Agency. New Zealand has Medsafe. 

The vaccine development and testing process

Developing a vaccine is done in phases. This usually takes close to a decade. For this vaccine, timelines have been shrunk by running phases simultaneously.

 Tests are done in animals, such as monkeys or mice, to see if the vaccine triggers an immune response.

 Tests done on a small number of people to test for an immune response, dosage and safety.

 Tests done on a larger number of people to test for immune response and safety.

 Tests done on thousands of people to see if the vaccine will protect against coronavirus. Traditionally people are split into two groups, some get a vaccine and others get a placebo. After a period of time both groups are checked to see if the vaccine protected against the virus. To get fast results it's best to test vaccines in areas where the virus is common.

 Vaccine approved for general usage. The US Food and Drug Administration has said it wants vaccines to be at least 50 percent effective in protecting against the virus. Comparatively a flu shot is usually 50 to 60 percent effective and the measles vaccine is 99 percent effective. 

The Covid-19 vaccine frontrunners

The following vaccines are the frontrunners. They are either in phase three trials or have limited approval for use. 

University of Oxford/AstraZeneca

Country: United Kingdom 
Vaccine platform: Non-Replicating Viral Vector
Doses: One

The much-touted University of Oxford/AstraZeneca ChAdOx1 vaccine has started phase three trials after earlier results showed a four-fold increase in antibodies for 95 percent of recipients after one month. The phase one and two trials were completed simultaneously.

Its phase three trial taking place in Brazil will have 2000 participants with an end date of October 2020. Another trial taking place in South Africa will also have 2000 participants. Early results are expected around November for the South African trial.

AstraZeneca has said its global supply capacity will exceed two billion doses per year by 2021. In June AstraZeneca's chief executive said it was on track to start delivering vaccines as soon as September, if trial results were successful. A vaccine manufacturer in India that is already manufacturing the vaccine said it should have 300 million doses ready by November.

SinoVac
 (Emergency use only - China)
Country: China
Vaccine platform: Inactivated
Doses: Two doses 14 days apart

SinoVac is developing CoronaVac and commenced a phase three trial in Brazil in July. The company said phase one and two trials have produced antibodies in 90 percent of people tested with no severe side effects. There are 8870 participants in the trial. The study completion date is listed as October 2021, but an interim efficacy analysis will be completed after 150 cases.

The private company has used similar technology to produce vaccines for hepatitis, swine flue, avian flu and the virus that causes hand, foot and mouth disease.

It's hoping to produce 300 million doses a year.

Moderna

Country: United States
Vaccine platform: Messenger RNA
Doses: Two doses 28 days apart

The new kid on the block is Moderna. It's never produced an approved vaccine and is using a technology which has never been used in an approved vaccine. One of the advantages to the technology is speed of production; unlike other types of vaccines, there's no need to grow the virus in chicken eggs from which to create a vaccine.

Phase one and two trials showed the vaccine produced an immune response. 

The phase three trial will involve 30,000 participants in the US. The study is due to be complete in October 2022. Early results should be known by November. 

Moderna says it's "on track" to deliver between 500 million and one billion doses per year from 2021.

Sinopharm/Wuhan Institute of Biological Products

Country: China
Vaccine platform: Inactivated
Doses: Two doses either 14 or 21 days apart

Sinopharm is investigating two inactivated virus vaccines. One with the Wuhan Institute of Biological Products and the other with the Beijing Institute of Biological Products. 

The lack of Covid-19 cases in China has meant Chinese companies need to run phase three trials outside China. This trial is being run in the United Arab Emirates. 

The company has said it expects the trial to take around three months and a vaccine could be available by the end of the year. It has the capacity to produce 100 million doses a year.

Sinopharm/Beijing Institute of Biological Products

Country: China
Vaccine platform: Inactivated
Doses: Two doses either 14 or 21 days apart

The second of Sinopharm's vaccines is also going through phase three trials in the United Arab Emirates.

It's been reported if the trial is successful the company has the capacity to produce 120 million doses annually.

Pfizer/BioNTech/Fosun Pharma

Country: Germany
Vaccine platform: RNA
Doses: Two doses 28 days apart

BioNtech has reported good immune response results and tolerable side effects from one of the vaccines it's been trialing. 

Pfizer will recruit around 30,000 participants for a phase two and three trial from the US, Argentina, Germany, and Brazil. If the trials are successful the companies hope to gain emergency use approval by the end of 2020. It aims to produce 1.3 billion doses by the end of 2021.

University of Melbourne/Murdoch Children’s Research Institute

Country: Australia
Vaccine platform: Live-attenuated vaccine
Doses: One

A vaccine developed a century ago is being investigated for use in the pandemic. Initially created for tuberculosis, the Bacillus Calmette-Guerins vaccine has been shown to reduce deaths in infants and reduce respiratory disease. It's not thought this vaccine will fully protect against Covid-19 but it may reduce the time a person is unwell. There's also a chance the effects of the vaccine may reduce quickly - possibly within three and 12 months. If it proves helpful against Covid-19 it may be a stop-gap measure which could better protect frontline workers until a targeted vaccine is completed.

A phase three trial is now underway in Australia and the Netherlands with health workers. 

CanSinoBIO
 (Limited approval only - China)
Country: China
Vaccine platform: Non-replicating viral vector
Doses: One

This is the only vaccine licensed for limited use. It was developed by a private company in partnership with China's Academy of Medical Sciences. In an unusual move, it was approved for emergency use after promising results in phase one and two trials.

It's approved for military use in China only. Any results from this use will not count as completing phase three trials. To get full regulatory approval a phase three trial will still need to take place. Phase three trials are taking place in Saudi Arabia and Pakistan, where 40,000 participants will be enrolled.

This vaccine looks to be less effective for people older than 55.

Gamaleya Research Institute
 (Conditional registration certificate - Russia)
Country: Russia
Vaccine platform: Non-replicating viral vector
Doses: Two

Courting controversy, this vaccine was approved for use in Russia before a phase three trial.

“I know that it works quite effectively, forms strong immunity, and I repeat, it has passed all the needed checks,” Russian President Vladimir Putin said.

Scientists worldwide were shocked at the approval before the vaccine had been tested in the usual way for safety and efficacy. "It is almost hard to know where to start with why this is so wrong: It is reckless, unethical, and now utterly reliant on dumb luck," said Petousis-Harris. The approval was later amended to a "conditional registration certificate" which means approval will occur if the phase three trial is successful.

It's a viral vector vaccine which uses two different adenoviruses. 

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