Experts Assess COVID-19 Vaccine Progress

Two human trials of COVID19 vaccines show they are both safe and induce a immune reaction, according to preliminary results. The first trial of the ‘Oxford vaccine’ uses a weakened chimpanzee common cold virus, that has been modified to include the SARS-CoV-2 spike protein. The vaccine was tested in 1,077 healthy adults and produced a strong antibody and T-cell response, with only mild side effects.

None of the subjects in either study were exposed to SARS-CoV-2 virus after vaccination, so it is not yet possible to determine whether the vaccines effectively protect against SARS-CoV-2 infection. 

Paul Griffin is Director of Infectious Diseases at Mater Health Services, Associate Professor of Medicine at the University of Queensland, and Medical Director and Principal Investigator at Q-Pharm, Nucleus Network.

“Basically, any COVID-19 vaccine that provides positive results in early phase trials is really good news. This tells us the vaccine has an acceptable safety profile and at least the preliminary laboratory testing of how well it works also suggests it may be effective. Both of these vaccines are very similar in that they are viral-vectored, meaning they use a live virus that does not cause clinical infection in humans to deliver the antigen.

In the case of the Oxford group, the fact the results are published in a highly-regarded, peer-reviewed journal adds credibility to the results presented. The study published in The Lancet overnight was a relatively large study involving over 1,000 participants, and they were able to conclude that the ChAdOx1 nCoV-19 vaccine had an acceptable safety profile, and that laboratory testing of the immune results showed that it generated an immune response from both of the major arms of the immune system, which definitely supports larger trials.

This response seemed to be boosted after the second dose. While the safety profile is acceptable, there was a statistically significantly higher rate of local and systemic reactions in the vaccine group, and in two of the five sites they added paracetamol pre-dose to reduce these.

The Chinese study has also been published in a highly regarded peer-reviewed journal, although it was a smaller study at 600 volunteers, and in this study only a single dose was utilised. This vaccine also induced a relatively high rate of solicited adverse events at over 70 per cent in both groups and severe adverse reactions in 9 per cent. The immunogenicity results presented suggested a good immune response also.

While these results are exciting and I agree with the conclusion that larger phase 3 studies are definitely supported by the information presented, we need to be cautious in overestimating the significance of these results. Even with very promising immunological results from early phase trials, sometimes this does not translate into actually protecting people from the infection as much as we need, which really needs to be proven and this is what the larger phase 3 trials will hopefully show us. These studies also only present relatively short-term data on the immune response, so we still do not know how long these will last.”

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Dr Rob Grenfell is CSIRO’s Health and Biosecurity Director.

“Preliminary findings from the Phase 1/2 trials of the University of Oxford’s vaccine candidates show encouraging results. The report shows the vaccine candidate generated an immune response, making antibodies and stimulating T-cells to fight COVID-19. We don’t know exactly what protects us against a coronavirus infection, as there is still so much we don’t know, so our research continues.

While the race for a vaccine against this virus is moving quicker than we’ve ever seen before, and the global need for a vaccine is evident, we can never forget safety is still of the highest importance.

While these are hopeful results, there’s still a long way to go before we have a viable vaccine at our fingertips.

We need to await the additional phase 3 clinical trials, which will study the potential vaccine candidate’s performance and safety.

These larger studies are conducted in broader populations in current disease outbreak sites, in this case South Africa, Brazil, and the UK. It won’t be clear if the vaccine candidate works, and is safe for the broader population, until these large-scale clinical trials are completed, and we can see through the randomised approach that the vaccinated group is protected.

We also need to determine the best way to administer the vaccine. As part of CSIRO’s preclinical study of Oxford’s vaccine candidate, our scientists evaluated the efficacy of one versus two doses as well as administration of the vaccine via a nasal delivery and/or an intramuscular injection.”

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Dr Trevor Drew, Director, CSIRO’s Australian Centre for Disease Preparedness (ACDP).

“CSIRO recently completed pre-clinical trials for two vaccine candidates, including Oxford’s ChAdOx1 nCoV-19, at ACDP, its high-containment facility in Geelong. These vaccine candidates were selected by the Coalition for Epidemic Preparedness Innovations (CEPI) in consultation with the World Health Organization, based on principles behind their design, the quality of their development, and their readiness for testing.

The pre-clinical testing at CSIRO started in March and involved obtaining and characterising SARS-CoV-2 – the causative virus of COVID-19 – and establishing a ferret model in which to test vaccines. A cohort of ferrets was vaccinated and, following a number of weeks to allow their immunity to develop, challenged with the virus. Researchers then assessed the efficacy of the vaccine candidates by characterising the immune response of the animals to the vaccines and comparing the level of protection between vaccinated and unvaccinated ferrets, as well as the different delivery methods and single versus double doses.

Early data from these trials has been shared with the University of Oxford. The results from this study are currently going through internal and external review, quality assurance, and a compliance audit. This is all part of the process of rigorously determining the safety and effectiveness of the vaccine candidate, to the standard required by licensing authorities. The results will be published following this review.”

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Professor Brian Oliver leads the Respiratory Molecular Pathogenesis Group at the University of Technology Sydney and the Woolcock Institute.

“Both studies have taken a similar approach towards developing a vaccine – they have taken what would typically be a harmless common cold virus, and genetically engineered the virus to produce proteins from the SARS-CoV-2 Virus (the virus that causes COVID-19). This might sound frightening but is a really common approach to producing vaccines.

These studies report on phase 2 clinical trial outcomes. In phase 2 trials some measure of the effectiveness (efficacy) of the drug or vaccine is made, and in these studies what had been measured is antibodies against SARS-CoV-2 in people that are vaccinated. Both studies are positive, immunised people do produce antibodies against SARS-CoV-2.

Am I excited – Yes! These studies do not show that vaccination prevents COVID-19, but show that vaccinated people do produce antibodies against the virus, and therefore it is likely that a vaccination would reduce the symptoms of a SARS-CoV-2 infection, just like the influenza vaccination does. What is now needed are large scale vaccination clinical trials to work out how effective these approaches are to protect people against developing COVID-19.”

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Dr Anthony Stowers is Vice President Recombinant Product Development at CSL.

“This is very encouraging early data and suggests that approaches being taken to target the ‘spike protein’ that is unique to coronavirus – such as the University of Oxford and the University of Queensland vaccines – are technically feasible.

As the authors of the Lancet paper note, there is now more work to do in assessing the vaccine’s effectiveness in a broader age population, including the important older age groups, as well as how persistent or lasting the immune response generated by the vaccine will be, and its effectiveness in preventing infection.”

Interest: CSL is partnering with the Coalition for Epidemic Preparedness Innovations (CEPI) and The University of Queensland (UQ) to accelerate the development, manufacture and distribution of a COVID-19 vaccine candidate. CSL is a Gold Sponsor of the AusSMC, contributing approximately 1% of our budget

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Professor Nigel McMillan is the Director in Infectious Diseases and Immunology at Menzies Health Institute Queensland, Griffith University.

“Today two clinical trials reported phase 1 results for vaccines to SARS-CoV-2, the virus that causes COVID-19. Phase 1 trials are the first stage of vaccine testing that test for safety and tolerability. Both the Oxford and CanSino vaccines use adenovirus technology to deliver part of a SARS-CoV-2 protein to the immune system, and both report good induction of B and T cell immunity (important for a strong overall immune response) and overall safety. Both also observed the usual and expected side effects of redness, fever, headache and swelling. Importantly both observed patients produced strong antibody responses that protected against the virus in lab tests.

Overall this is an important step forward in the vaccine development pipeline. The next phase will be to vaccinate larger groups of people to further examine safety, but more importantly this should be undertaken in areas with high virus load to test whether there is any protection against disease. The other important issue to keep following the phase 1 patients to see how long the vaccine responses last as this will be critical in developing our long term response.”