More than 200 vaccines against COVID-19 are in development worldwide. Australia has signed supply agreements with 4 manufacturers – if their vaccines are proved safe and effective (see Table). In addition, as part of the COVAX Facility (a global vaccines scheme), Australia should also have access to a portfolio of vaccines, including the Moderna vaccine.
What technology do the vaccines use?
Of the three vaccines that have released results so far – two of the vaccines (Pfizer’s vaccine and Moderna’s vaccine) use a new technology involving messenger RNA (mRNA).
Instead of containing antigens like traditional vaccines, mRNA vaccines deliver the genetic material that codes for specific viral proteins, encapsulated in a lipid nanoparticle. In this case, the mRNA that codes for the SARS-CoV-2 spike protein – the protein which enables the virus’ entry into host cells. The host cells are tricked into manufacturing the spike protein, which then triggers an immune response in the host against the SARS-CoV-2 virus.
These COVID-19 mRNA vaccines will be the first vaccines ever approved to use mRNA technology in humans.
The Oxford vaccine uses a chimpanzee common cold virus (an adenovirus) modified so that it cannot cause infection in humans and then programmed to contain the genetic instructions for the spike protein.
The Novavax vaccine contains purified pieces of the SARS-CoV-2 spike protein (made by moth cells), administered with an adjuvant.
The University of Queensland / CSL vaccine uses molecular clamp technology to lock the unstable SARS-CoV-2 spike protein into a shape and prevent it from uncoiling. Then the protein is purified and manufactured into a vaccine. This then enables the immune system to recognise the spike protein and respond more effectively. The vaccine also contains an adjuvant.
How promising do the vaccines look?
Three of Australia’s options have recently reported very promising results – the Pfizer / BioNTech vaccine, the Moderna vaccine (available via COVAX), and the Oxford University/ AstraZeneca vaccine. The results so far have been announced only by press releases – to date none have been published in peer reviewed journals.
The results have not been without some controversy – at least regarding reporting of the Oxford / AstraZeneca vaccine’s efficacy. Clarity is expected later this week upon publication of the full data in the Lancet.
Issue no 1 with the Oxford / AZ vaccine was the difference in efficacy of the vaccine with different regimens – a reported 62 per cent when 2 full doses were given; and 90 per cent when a half dose was followed by a full dose a month later. This raised questions – further amplified by reports that the half-dose/full-dose regimen was in fact an accident caused by a manufacturing error.
A proposed rationale for the poorer response with the full-dose/full-dose regimen is that this dose regimen causes greater immunity to the chimpanzee carrier virus, thus rendering the second dose less effective.
Since then the company has indicated they will have to validate the results with a further study.
Issue no 2 was the pooling of the results from these two different clinical trials – giving a meaningless average efficacy of 70% which doesn’t represent either dosing regimen.
The Pfizer / BioNTech vaccine has reported a 95% efficacy beginning 28 days after the first dose. In adults over 65 years of age, observed efficacy was over 94%.
Moderna’s vaccine has reported a similar efficacy of 94.5% in the so-called COVE study.
These results are independently reviewed by a board appointed by the National Institutes of Health. Moderna plans to submit COVE study data to a peer-reviewed journal.
University of Queensland’s molecular clamp vaccine is still in Phase 1 clinical trials. Pre-clinical testing in small animal models showed it had the ability to raise high levels of neutralising antibodies.
The Novavax vaccine has been shown in Phase 1/2 clinical trials to be well-tolerated in healthy adults aged 18 to 59 and to produce antibody responses equalling or exceeding those in COVID-19 patients. Phase 3 trials are underway in the UK.
Controversy aside, to get efficacy rates over 90 per cent puts a vaccine in the same basket as some of our most effective vaccines for other diseases. For perspective, the US Food and Drug Administration has set the bar at 50% efficacy for a COVID-19 vaccine, on the premise that even that will make a difference.
|COVID-19 vaccines Australia has supply agreements for|
|Vaccine||Technology||Number of doses||Efficacy||Trial participants|
|Pfizer / BioNTech||mRNA||2 doses||95% efficacy. Observed efficacy in adults over 65 years >94%||More than 43,000|
|Moderna (via COVAX Facility)||mRNA||2 doses||94.5% efficacy||30,000|
|Oxford University / AstraZeneca||Viral vector vaccine||2 doses||2 Full doses: 62% efficacy
Half-dose, full-dose: 90% efficacy
Full results awaited – due to be published in Lancet
|Novavax||Protein subunit vaccine||Likely 2 doses||Currently in Phase 3 trials in UK||15,000 (Phase 3)|
|University of Queensland / CSL||Protein vaccine||Likely 2 doses||Currently in Phase 1 clinical trials in Australia||120|
|COVAX Facility||Portfolio of 10 different vaccines||Various||Various stages from Preclinical to Phase 3 trials|
Efficacy in older age groups
How effective the vaccines will be in real life, as compared with their efficacy in clinical trials, will only be answered once they are in widespread use. In trials, results in older age groups have been promising.
The Pfizer / BioNTech vaccine is being tested in adults 18-54 years of age, adults 55-85 years and adolescents 12-18 years. Their press release reported that efficacy was consistent across age groups – observed efficacy in adults over 65 years was more than 94%.
Moderna’s vaccine has been tested in more than 7000 Americans over the age of 65 and 5000 under 65 with high risk chronic diseases. It appears to be safe and effective in older adults.
The Oxford / AstraZeneca vaccine had similar immunogenicity across different age groups, but was better tolerated by older adults. Antibody levels were boosted and maintained at 28 days after the booster dose, including in the 70 years and over group. T-cell responses in older adults were encouraging, the Oxford Vaccine Group said.
Safety and side effects
It’s possible that with the mRNA vaccines, the rate of severe reactions will be higher than for seasonal flu vaccines, and although transient, reactions may be intense.
Pfizer / BioNTech vaccine – reported to be well tolerated in all populations; no serious safety concerns. Fatigue (3.8%) and headache (2.0%) were the only Grade 3 adverse events greater than 2% in frequency.
Moderna – Grade 3 events greater than 2% in frequency after the first dose included injection site pain (2.7%). After the second dose, they included fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%) and erythema/redness at the injection site (2%). These were generally short-lived.
Oxford / AstraZeneca – No serious safety events related to the vaccine have been identified, according to AstraZeneca’s press release. In earlier testing of the chimpanzee adenovirus vector for use in potential Ebola and Zika virus vaccines, there were no serious side effects.
With the coronavirus vaccine, injection site pain and tenderness were the most common local adverse reactions. Fatigue, headache, feverishness and myalgia were the most common systemic adverse reactions. Most of the reported adverse events were mild to moderate in severity. Adverse reactions were less to the booster dose than the prime dose. Also, the lower dose of vaccine was less reactogenic than the standard dose.
How long will immunity last?
It’s not yet known how long the vaccines might offer protection for. And whether regular boosters will be needed.
In people who have been infected with COVID-19, Monash University researchers have shown (in a preprint study) that immunity lasts up to 8 months, giving hope that a vaccine could give long-term protection.
It’s also not known whether the vaccines only prevent people from getting sick from the virus, or whether they actually prevent the virus being transmitted. These are questions which won’t be answered until further down the track.