November 11, 2020
Clinicians and scientists from WIMR and the Westmead Health Precinct answer some of the most important questions about COVID-19 vaccines.
Recent local and international reports of promising COVID-19 vaccine trials are being cautiously welcomed. However, with so many potential vaccines in the news, it can be difficult to understand what it all means.
Luckily, the Westmead Health Precinct is home to some of Australia's leading virus experts. They sat down to answer the most commonly asked questions about potential COVID-19 vaccines, and how a successful vaccine could be rolled out in Australia.
1. When will a vaccine be available in Australia?
The target is early to mid-2021 - subject to the Therapeutic Goods Administration (TGA) registering a vaccine as being safe and effective, and under the advice of the relevant medical authorities (these will include ACV – the Advisory Committee on Vaccines, AHPPC, CDNA, the State Departments of Health etc.)
2. How many vaccines will there be in Australia in 2021? What are their differences?
Vaccines in phase 3 trials which are expected to be registered as safe and effective in Australia are likely to include up to two protein-based vaccines
, one messenger ribonucleic acid (mRNA
), and one viral vector type vaccine
. Other vaccine types will be considered as data becomes available.
Currently, there are over 50 different COVID-19 vaccines in clinical trial, 11 of which are undergoing phase 3 clinical trial and many more in pre-clinical assessment. Four of the vaccine candidates undergoing Phase 1 trials are in Australia, one in each of Sydney, Melbourne, Adelaide and Perth.
Various methods have been used to produce a vaccine, with the aim of producing a safe and effective immune response to SARS-CoV-2. The production of these vaccine types varies, but they all introduce SARS-CoV-2 antigen(s) into the body to which the immune system produces antibodies or cellular responses.
Data on the effectiveness and safety of these vaccines to support their use in the general population is pending. These data will guide decisions whether multiple doses are required, their timing, and need for re-vaccination over time (eg. annually).
A live attenuated virus is constructed by in vitro
mutating the original virus to create a ‘weaker’ virus that infects the recipient but does not cause significant harm. Examples include measles and mumps vaccines.
Inactivated virus vaccines are produced by disabling a virus through radiation, chemicals or heat: the inactivated virus cannot cause disease as it does not replicate. Examples include hepatitis A and rabies vaccines.
A protein subunit vaccine contains a subunit of the virus antigen to which the immune system is active. As the virus is incomplete, it cannot replicate and cause disease. Examples include the shingles and hepatitis B vaccines.
Virus-like particle vaccines closely resemble the virus in structure but contain none of its genetic material, meaning it cannot replicate in the host. An example is the papillomavirus vaccine.
DNA and RNA vaccines consist of viral messenger RNA (mRNA) or DNA code for a viral protein. This code is inserted into a human cell which then produces the viral protein antigen that is recognised by the immune system. These vaccines are not yet approved for human use, but have been trialled for various pathogens including Zika, HIV, and influenza.
Like DNA and RNA vaccines, viral vector vaccines contain genetic code for making a viral antigen which is introduced into human cells by a harmless virus like adenovirus. These types of vaccines are not yet approved for human use.
3. How often will vaccines be required?
Initial vaccination may involve one or two doses, depending on the vaccine type. Whether vaccination is needed once, or annually (as is the case for the flu vaccine) is unknown, and will depend on vaccine trial data, community patterns of disease, and laboratory measures of vaccine immunity.
4. What level of efficacy will the TGA require to approve each vaccine?
The TGA assesses safety, quality and efficacy in clinical trials; monitors manufacturing quality standards of vaccines, and monitors vaccines for safety after their supply in Australia. The TGA's decision as to whether to register a vaccine for use in Australia is informed by the advice of the Advisory Committee on Vaccines (ACV)
US, European, UK and Australian regulatory agencies (FDA, EMA, MHRA and TGA) have mandated 50% as minimum efficacy for licensure. FDA also wants half of phase 3 trial subjects (~30-40k) to undergo two months of safety monitoring after vaccine administration. Generally the TGA follows FDA’s advice.
5. Who will provide these vaccines?
CSL Limited (Seqirus) will provide a University of Queensland protein vaccine to supply 51 million doses from its Melbourne production facility.
Novavax will provide a protein vaccine to supply 40 million vaccine doses in Australia per annum containing an adjuvant (Matrix-M) which enhances the immune response.
AstraZeneca will provide an Oxford University Viral Vector vaccine to supply 33 million doses in Australia per annum.
Pfizer/BioNTech will provide an mRNA vaccine to supply 10 million vaccine doses in Australia per annum.
The above vaccines will be provided based on TGA approval of efficacy and safety data.
6. What is the significance of Pfizer’s announcement on 9 November 2020?
On 9 November Pfizer announced its first interim efficacy analysis from its Phase 3 mRNA-based vaccine candidate, BNT162b2, conducted by an external independent data monitoring committee.
The vaccine candidate was found to be more than 90% effective in preventing COVID-19 in participants without evidence of prior infection. The analysis evaluated 94 confirmed cases of COVID-19 in trial participants. The study enrolled 43,538 participants with 42% having diverse backgrounds, and no serious safety concerns were observed; safety and additional efficacy data continued to be collected.
Submission for Emergency Use Authorization (EUA) to the FDA is planned for soon after the required safety milestone is achieved, which is currently expected to occur in the third week of November.
The clinical trial will continue to final analysis at 164 confirmed cases in order to collect further data and characterize the vaccine candidate’s performance against other study endpoints.
7. How many Australians could be vaccinated in 2021?
The goal and the expectation is that Australians who seek vaccination will be vaccinated within 2021.
8. Which Australians will be first vaccinated?
The first 1.5 million people to be vaccinated will comprise health and aged care workers, the elderly and vulnerable and those working in services critical to society functioning. These indications are being refined by State and National governments.
In the case of the elderly and vulnerable, efficacy is likely to be lower.
9. Who is involved in planning for the initial rollout?
The Australian Government is currently consulting with the states and territories, key medical experts and industry peak bodies on the framework for the initial roll-out of the COVID-19 vaccination program.
10. Where will be the locations of places of vaccination?
Key vaccination sites will initially include GPs, GP respiratory clinics, state and territory vaccination sites and workplaces such as aged care facilities.
11. Will the vaccine be voluntary? Will it be free?
Australia has a world class vaccination program with world leading vaccination rates. The COVID-19 vaccine will not be mandatory and individuals will maintain the option to choose not to vaccinate. The vaccine will be available for free to those who choose to be vaccinated.
Latest figures suggest at best 80% may choose to be vaccinated.
The vaccine will be free for all Australians.
12. Will other vaccines be available to Australians?
Australia has also joined the COVAX facility, which will provide access to a large portfolio of COVID-19 candidates and manufacturers around the world.
13. Will Australian produced vaccines be distributed to our neighbours?
The Australian Government has also committed to support access to safe and effective COVID-19 vaccines for the Pacific and Southeast Asia, as part of a shared recovery for our region from the pandemic, as well as $80 million to the international COVAX Facility for the benefit of high-risk populations in developing countries. Our agreements allow Australia to donate to partners in the Pacific and Southeast Asia, should these vaccines prove safe and effective, and units are available above domestic needs.
14. What are the logistical challenges for the roll-out?
The roll-out of a potential COVID-19 vaccine is a significant logistical challenge. Suppliers that have a proven track record in vaccine logistics (including cold-chain) and distribution or booking systems, tracking and reporting of vaccines are being invited to participate in a limited tender process.
The RNA vaccines need at least dry ice for distribution once the vaccine is taken out of -80 freezers.
15. What records of vaccination will be kept?
As part of our COVID-19 vaccines strategy and broader vaccines strategy, the Australian Government is considering an amendment to the Australian Immunisation Register Act 2015 to mandate reporting of all vaccinations to the Register.
16. Where can I access further vaccine information?
For the latest COVID-19 vaccine information visit: health.gov.au (https://www.health.gov.au/resources