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EXPERT REACTION: Two COVID-19 vaccine trials show promise

Embargoed until: Publicly released:
Peer-reviewed: This work was reviewed and scrutinised by relevant independent experts.

Randomised controlled trial: Subjects are randomly assigned to a test group, which receives the treatment, or a control group, which commonly receives a placebo. In 'blind' trials, participants do not know which group they are in; in ‘double blind’ trials, the experimenters do not know either. Blinding trials helps removes bias.

People: This is a study based on research using people.

The Lancet has published two separate research trials as part of the global race to find a COVID-19 vaccine. In both cases, participants were given a genetically modified common cold virus, aimed at inducing an immune response to "prepare" the body for COVID-19. The first was led by University of Oxford researchers who tested their vaccine on more than 1,000 people in the UK. Compared to the control group (given a meningitis vaccine), the SARS-CoV-2 vaccine caused minor side effects more frequently, but some of these could be reduced by taking paracetamol, and there were no serious adverse events. In the second trial led by Chinese researchers with more than 500 participants, people who were given the trial vaccine had a much higher rate of adverse effects than the placebo group. Most of the negative side effects were mild or moderate and the most common severe reaction was fever. Both teams report their vaccines produced an immune response in their subjects, but they say more research is needed to know whether they can actually stop COVID-19 infection.

Journal/conference: The Lancet

DOI: 10.1016/S0140-6736(20)31604-4

Organisation/s: University of Oxford, UK; Jiangsu Provincial Center of Disease Control and Prevention, China

Funder: Oxford vaccine: This study was funded by UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen. It was conducted by researchers from University of Oxford, NIHR Oxford Biomedical Research Centre, Philipps University of Marburg, University Hospital Southampton NHS Foundation Trust and University of Southampton, University of Bristol, National Infection Service, Public Health England, St George’s University, University Hospitals Bristol and Weston NHS Foundation Trust, Imperial College London. NOTE: Full list of declaration of interests for the authors are provided in the paper. China vaccine: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics. WC reports grants from the National Key R&D Program of China (2020YFC10841400), and grants from the National Science and Technology Major Project (2016ZX10004001, 2018ZX09201005). J-BG is an employee of CanSino Biologics. All other authors declare no competing interests.

Media release

From: The Lancet

The Lancet: UK’s vaccine against SARS-CoV-2 is safe and induces an immune reaction, according to preliminary results

Promising early stage results from a phase 1/2 clinical trial of the UK’s vaccine candidate against SARS-CoV-2 (the virus that causes COVID-19) are published today in The Lancet.

The early stage trial finds that the vaccine is safe, causes few side effects, and induces strong immune responses in both parts of the immune system – provoking a T cell response within 14 days of vaccination (ie, a cellular immune response, it could find and attack cells infected with the virus), and an antibody response with 28 days (ie, humoral immune response, it could find and attack the virus when it was circulating in the blood or lymphatic system).

An ideal vaccine against SARS-CoV-2 should be effective after one or two vaccinations, work in target populations including older adults and those with other health conditions, confer protection for a minimum of six months, and reduce onward transmission of the virus to contacts. The current trial is too preliminary to confirm whether the new vaccine meets these requirements, but phase 2 (in the UK only) and phase 3 trials to confirm whether it effectively protects against SARS-CoV-2 infection are happening in the UK, Brazil and South Africa.

Explaining how the vaccine works, study lead author Professor Andrew Pollard, University of Oxford, UK, says: “The new vaccine is a chimpanzee adenovirus viral vector (ChAdOx1) vaccine that expresses the SARS-CoV-2 spike protein. It uses a common cold virus (adenovirus) that infects chimpanzees, which has been weakened so that it can’t cause any disease in humans, and is genetically modified to code for the spike protein of the human SARS-CoV-2 virus. This means that when the adenovirus enters vaccinated people’s cells it also delivers the spike protein genetic code. This causes these people’s cells to produce the spike protein, and helps teach the immune system to recognise the SARS-CoV-2 virus.” [1]

He continues: “The immune system has two ways of finding and attacking pathogens – antibody and T cell responses. This vaccine is intended to induce both, so it can attack the virus when it’s circulating in the body, as well as attacking infected cells. We hope this means the immune system will remember the virus, so that our vaccine will protect people for an extended period. However, we need more research before we can confirm the vaccine effectively protects against SARS-CoV-2 infection, and for how long any protection lasts.” [1]

The new trial included 1,077 healthy adults aged 18-55 years with no history of COVID-19, and took place in five UK hospitals between 23 April and 21 May 2020 [2]. The data included in the paper covered the first 56 days of the trial and is ongoing.

The participants either received the new COVID-19 vaccine (543 people) or the meningococcal conjugate vaccine (534 people). 113 participants (56 given the COVID vaccine, and 57 in the control group) were also asked to take paracetamol before and for 24 hours after their vaccination to help reduce vaccine-associated reactions (as the COVID-19 vaccine was given in a high dose to help induce a strong immune response).

All participants gave additional blood samples and underwent clinical assessments to determine if the vaccine was safe and whether it provoked an immune response. Participants were also asked to record any adverse events throughout the trial.

The participants were split into four groups. Group 1 (88 people) had additional safety monitoring to form the phase 1 part of the trial, and had antibody and T cell responses assessed. Group 2 (412 people) had extra blood taken to assess for antibody and T cell responses, and group 4 (567 people) had serum taken to assess for antibody response only. In groups 1, 2 and 4 half the participants received the COVID-19 vaccine and half received the control vaccine. Group 3 (10 people) received only the COVID-19 vaccine, and were given an extra dose of vaccine 28 days after the first dose to determine safety and whether this boosted antibody and T cell responses.

The vaccine was found to have an acceptable safety profile and there were no serious adverse events. Fatigue and headache were the most commonly reported reactions (around 70% [340/487] of all participants given the COVID-19 vaccine only reported fatigue, and 68% [331/487] reported headache, compared with around 48% [227/477] and 41% [195/477], respectively, of participants in the control group without paracetamol). Other common side effects included pain at the injection site, muscle ache, malaise, chills, feeling feverish, and high temperature.

Participants taking paracetamol around their vaccination had reduced pain, chills, feeling feverish, muscle ache, headache, and malaise in the two days following vaccination. In addition, in the 10 people who received the extra dose of the COVID-19 vaccine, side effects were less common after the second dose.

The authors found that there were strong antibody and T cell responses from the vaccine. T cell responses targeting the SARS-CoV-2 spike protein were markedly increased (in the 43 participants studied), peaking 14 days after vaccination (median 856 spot-forming cells per million peripheral blood mononuclear cells), with this level declining slightly by day 56 of the trial (to median 424 spot-forming cells per million peripheral blood mononuclear cells) . The T cell response did not increase with a second dose of the vaccine, which is consistent with other vaccines of this kind.

Antibody responses peaked by day 28 (median 157 ELISA units – studied in 127 participants) and remained high until the measurement at day 56 in the trial (median 119 ELISA units – studied in 43 participants) for those given a single vaccine. This response was boosted by a second dose (median 639 ELISA units at day 56 in these 10 participants).

28 days after vaccination, neutralising antibody responses against SARS-CoV-2 were detected in 32 of 35 participants (91%) (when measured in MNA80 neutralisation assay), and in 35 of 35 participants (100% - when measured in PRNT50 neutralisation assay) who received a single dose of the COVID-19 vaccine. These responses were present in all participants who had a booster dose of the vaccine (nine of nine participants in MNA80 assay at day 42, and ten of ten in Marburg VN assay on day 56).

The authors found that taking paracetamol did not affect immunogenicity of the COVID-19 vaccine.

Co-author, Professor Sarah Gilbert, University of Oxford, UK, says: “There is still much work to be done before we can confirm if our vaccine will help manage the COVID-19 pandemic, but these early results hold promise. As well as continuing to test our vaccine in phase 3 trials, we need to learn more about the virus – for example, we still do not know how strong an immune response we need to provoke to effectively protect against SARS-CoV-2 infection. If our vaccine is effective, it is a promising option as these types of vaccine can be manufactured at large scale. A successful vaccine against SARS-CoV-2 could be used to prevent infection, disease and death in the whole population, with high risk populations such as hospital workers and older adults prioritised to receive vaccination.” [1]

The authors note some limitations, including that more research is needed to confirm their findings in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations. The authors note that these groups are being recruited in their ongoing phase 2 and 3 trials of the vaccine in the UK, Brazil and South Africa. In the current trial, 91% (979/1,077) of participants were white and the average age of participants was 35 years.

They also note that a small number of participants had detectable neutralizing antibodies and T cell responses against SARS-CoV-2 spike protein before vaccination, likely to be due to past asymptomatic infection as potential participants with recent COVID-19-like symptoms or with a history of positive PCR test for SARS-CoV-2 were excluded from the study.

The authors say the participants recruited in this study will be followed-up for at least one year to continue to study the vaccine’s safety and the immune response it provokes.

Writing in a linked Comment discussing both Articles, lead author Assistant Professor Naor Bar-Zeev (who was not involved in the two studies), International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, USA, says: “These trial reports are hugely anticipated. The results of both studies augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety… Both trials used adenovirus vectors to deliver and study the COVID-19 vaccine, an innovative and efficient means of vaccine development in the midst of a pandemic. Capable of generating humoral, cellular, and innate responses, adenovirus vectored vaccines have much potential.”

However, he warns of the preliminary nature of the two vaccine candidates. He continues: “The platform [adenovirus vectored vaccines] only achieved European Commission regulatory licensure on July 1, 2020, with the Ebola vaccine. Much remains unknown about these and other COVID-19 vaccines in development, including longevity of response and immunogenicity in older adults or other specific groups, such as those with comorbidities who are often excluded from clinical trials, or ethnic or racial groups more severely affected by COVID-19.”


The Lancet: Chinese phase 2 trial finds vaccine is safe and induces an immune response

A phase 2 trial of an Ad5 vectored COVID-19 vaccine candidate, conducted in China, has found that the vaccine is safe and induces an immune response, according to new research published in The Lancet.

The randomised trial sought to evaluate the safety and immunogenicity of the vaccine candidate and follows a phase 1 trial published in May 2020 [1]. The results provide data from a wider group of participants than their phase 1 trial, including a small sub-group of participants aged over 55 years and older, and will inform phase 3 trials of the vaccine.

However, the authors note that it is important to stress that no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine whether the vaccine candidate effectively protects against SARS-CoV-2 infection.

Professor Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, China, says: “The phase 2 trial adds further evidence on safety and immunogenicity in a large population than the phase 1 trial. This is an important step in evaluating this early-stage experimental vaccine and phase 3 trials are now underway.” [2]

Currently, there are about 250 candidate vaccines against SARS-CoV-2 in development worldwide, including mRNA vaccines, replicating or non-replicating viral vectored vaccines, DNA vaccines, autologous dendritic cell-based vaccine and inactive virus vaccines. At least 17 of them are currently under evaluation in clinical trials.

The vaccine in this trial uses a weakened human common cold virus (adenovirus, which infects human cells readily but is incapable of causing disease) to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.

508 participants took part in the trial of the new vaccine. Of these, 253 received a high dose of the vaccine (at 1×1011 viral particles/1.0mL), 129 received a low dose (at 5×1010 viral particles/1.0mL) and 126 received placebo. Approximately two thirds of participants (309; 61%) were aged in 18-44 years, a quarter (134; 26%) were aged 45-54 years, and 13% (65) were 55 years or older.

Participants were monitored for immediate adverse reactions for 30 minutes after injection and were followed for any injection-site or systemic adverse reactions within 14- and 28-days post-vaccination. Serious adverse events reported by participants during the whole study period were documented. Blood samples were taken from participants immediately before the vaccination and 14- and 28-days post-vaccination to measure antibody responses.

The trial found that 95% (241/253) of participants in the high dose group and 91% (118/129) of the recipients in the low dose group showed either T cell or antibody immune responses at day 28 post-vaccination.

The vaccine induced a neutralising antibody response in 59% (148/253) and 47% (61/129) of participants, and binding antibody response in 96% (244/253) and 97% (125/129) of participants, in the high and low dose groups, respectively, by day 28. The participants in the placebo group showed no antibody increase from baseline.

Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with geometric mean titres of 19.5, and 18.3 in participants receiving the high and low dose, respectively. The binding antibody response peaked at 656.5 ELISA units and 571 ELISA units for the high and low dose of the vaccine, respectively.

T cell responses were also found in 90% (227/253) and 88% (113/129) of participants receiving the vaccine at high and low dose, respectively. A median of 11 spot-forming cells and 10 spot-forming cells per 1 × 10⁵ peripheral blood mononuclear cells in participants in the high dose and low dose groups, respectively, were observed at day 28.

The proportions of participants who had any adverse reactions such as fever, fatigue and injection-site pain were significantly higher in vaccine recipients than those in placebo recipients (72% [183/253] in the high dose group, 74% [96/129] in the low dose group, 37% [46/126] in the placebo group). However, most adverse reactions were mild or moderate. Within 28 days, 24 (9%) participants in the high dose group had severe (grade 3) adverse reactions, which was significantly higher than in those receiving the low dose or placebo (one (1%) participant in the low dose group, and 2 people (2%) in the placebo group). The most common severe reaction was fever.

The authors note that pre-existing immunity to the human adenovirus which was used as the vector (ie, the Ad5 vector) for this vaccine and increasing age could partially hamper the specific immune responses to vaccination, particularly for the antibody responses. Among the 508 participants, 266 (52%) participants showed a high pre-existing immunity to Ad5 vector, while 242 (48%) had low pre-existing immunity to Ad5 vector. Those with a higher pre-existing anti-Ad5 immunity showed an inferior immune response (the binding and neutralising antibody levels were around two times larger in people with low pre-existing anti-Ad5 immunity, compared to those with high pre-existing immunity). Compared with the younger population, older participants generally had significantly lower immune responses and higher tolerability to the Ad5 vectored COVID-19 vaccine.

Professor Wei Chen, Beijing Institute of Biotechnology, China, says: “Since elderly individuals face a high risk of serious illness and even death associated with COVID-19 infection, they are an important target population for a COVID-19 vaccine. It is possible that an additional dose may be needed in order to induce a stronger immune response in the elderly population, but further research is underway to evaluate this.” [2]

The authors note that the trial was conducted in Wuhan, China, and the baseline immunity is representative of Chinese adults at that time, but other countries may have different rates of immunity which should be considered. Additionally, the trial only followed participants for 28 days and no data about the durability of the vaccine-induced immunity is available from this study. Importantly, no participants were exposed to SARS-CoV-2 virus after vaccination, so it is not possible for this study to determine the efficacy of the candidate vaccine or any immunological risk associated with antibody induced by vaccination when having a virus exposure.

Attachments:

  • The Lancet
    Web page
    Oxford vaccine paper
  • The Lancet
    Web page
    China vaccine paper
  • The Lancet
    Web page
    China and Oxford vaccines - The Lancet commentary
  • UK Science Media Centre
    Web page
    UK Science Media Centre press briefing on Oxford vaccine - audio
  • UK Science Media Centre
    Web page
    UK Science Media Centre press briefing on Oxford vaccine - video
  • UK SMC
    Web page
    UK SMC Expert Reaction

Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Professor Johnson Mak is a Professor at the Institute for Glycomics, Griffith University

It is certainly encouraging to see the early stage of vaccine trail can elicit immune response, and these are steps in the right direction. The precise abilities of these vaccine candidates to protect people effectively across large population remain to be determined.

Regardless of potential outcomes of clinical trials with these vaccine candidates, public should be mindful that SARS-CoV-2 is likely to be with us for a long time. In the mean time, the preventive measures in which Australian government (both Federal and States) have implemented, (including social distance; isolation; and mask [or alike]) should be observed to maximise our capacity to avoid overwhelming our hospital system.

Last updated: 23 Jul 2020 9:44am
Declared conflicts of interest:
None declared.

Prof Chris Goodnow is the Executive Director of the Garvan Institute of Medical Research

The virus-neutralising antibody levels induced by the Oxford or Chinese vaccines are worryingly low. They are even less than the relatively low antibody levels in people who have had the virus itself.

The Oxford group already has other evidence out online but not yet peer reviewed, that these levels are not sufficient to protect against SARS-CoV-2 infection.

While as a community member I remain optimistic, as a scientist the evidence looks much less so.

Last updated: 21 Jul 2020 3:20pm
Declared conflicts of interest:
None declared.
Associate Professor Ian Mackay is a clinical virologist at the University of Queensland

On the Oxford vaccine trial:

The early results look really, really encouraging with both the antibody and cellular arms of the immune response triggered by the SARS-CoV-2 Spike protein component to produce what could be protective immunity when tested in areas with viral spread.

The safety profile found no severe side-effects.

I think this gives us all hope but it remains a small trial on which to build. Next will be a bigger trial in which we'd hope to see some less healthy, older and much more diverse vaccines - more reflective of the group most at risk of severe disease and death. This is the group in which we really need to see good protection from any vaccine. Unfortunately and also, fortunately, there are many places worldwide with lots of cases so that effect should be relatively quick to see in future trials. We can't yet tell how long these responses will last because this study, and the pandemic itself, have not been active for long enough to get that sort of detail yet. Because of that, it's also good news that previous studies found immunity which developed to the chimpanzee adenovirus component of a related influenza vaccine didn't affect the immune response to the influenza part, and preliminary work here similarly showed a second dose boost the initial dose's important antiviral immune response. If multiple doses of the vaccine are needed, this is important to know.

 

Last updated: 21 Jul 2020 1:50pm
Declared conflicts of interest:
None declared.

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

Last updated: 21 Jul 2020 1:25pm
Declared conflicts of 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 also a gold supporter of the AusSMC who owns and operates Scimex
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.

Last updated: 21 Jul 2020 12:32pm
Declared conflicts of interest:
Paul is running a number of Covid-19 vaccine studies (Novavax and UQ)
Professor Bruce Thompson is Dean of the School of Health Sciences at Swinburne University

Both of these studies are good news and encouraging. The data demonstrated that there was an immune response to the vaccine. There are still a number of unanswered questions before these vaccines will be ready for use in large populations, however it is very encouraging that these preliminary studies demonstrated a response

Last updated: 21 Jul 2020 12:32pm
Declared conflicts of interest:
None declared.
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.

Last updated: 21 Jul 2020 12:30pm
Declared conflicts of interest:
CSIRO conducted animal trials of the Oxford vaccine
Dr Trevor Drew is Director of 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

Last updated: 21 Jul 2020 12:28pm
Declared conflicts of interest:
CSIRO conducted animal trials of the Oxford vaccine
Associate Professor Siouxsie Wiles is a microbiologist in the Faculty of Medical and Health Sciences at University of Auckland

The two new Lancet papers describe the results of early human trials of two of the 150 candidate COVID-19 vaccines currently under development - the Oxford/AstraZeneca vaccine candidate (ChAdOx1) and the Beijing Institute of Biotechnology/CanSino Biologics Ad5-vectored candidate. Both these vaccines are based on weakened forms of cold viruses (adenoviruses) that aren’t able to replicate in human cells and which have been engineered to express the spike protein from the COVID-19 virus. The Oxford/AstraZeneca vaccine uses an adenovirus originally from chimps and the Beijing Institute/CanSino vaccine uses a human adenovirus.

The trials show that both the Oxford/AstraZeneca vaccine and the Beijing Institute/CanSino vaccine are safe over the short term and that the majority of healthy people vaccinated mount an immune response. This is very promising news but doesn’t mean we should be expecting a vaccine to be widely available anytime soon. The next step is to find out whether either of the candidates protects people against COVID-19. Studies to find this out for the Oxford/AstraZeneca vaccine are now underway in Brazil, the UK, and South Africa. These are designed to take a year but I imagine if they look promising we’ll hear much sooner than that.

Last updated: 21 Jul 2020 12:13pm
Declared conflicts of interest:
No conflict of interest.
Associate Professor Helen Petousis-Harris, Vaccinologist, University of Auckland

In order to be effective, vaccines need to elicit the right type of immune response against the right targets. In the case of COVID-19, most vaccines are targeting what is called the spike protein, which the virus uses to gain entry into our cells and infect them. Last week early results from the Moderna mRNA vaccine were published, indicating that a broad immune response against the virus’s spike protein was triggered. This week data from both the Oxford viral vector vaccine and a viral vector vaccine from CanSino in China also indicate good immune responses are generated.

While the Oxford and CanSino vaccines are both viral vector vaccines, the viruses used to carry the SARS-COVID-19 spike protein gene are different. While the Oxford vaccine uses a virus that does not normally infect humans, the Chinese version uses a virus that does commonly infect humans. There is a possibility that vaccines made with the human virus may be less effective because some people may already be immune to them.

There are no serious safety concerns noted with these vaccines at this stage. It should be expected that some people will experience symptoms consistent with making a nice immune response. Other than pain and redness at the site of infection, this includes headache and fever - duration is short. Providing these events are not too severe it can be seen as a sign of the body making immunity.

There are recent reports suggesting protection from a COVID-19 vaccine may be brief. These are largely based on recovered cases where antibodies are observed to wane. This does not mean that these people are not still protected and it does not mean that vaccine protection might be short-lived. There are a number of mechanisms involved in protection that we are not measuring and, with respect to COVID-19, do not yet fully understand.

Ultimately we will only know the effectiveness of these vaccines once they have been through the next phases of study and the rates of COVID-19 in people who received the vaccine can be compared with the rates in people who received a placebo (no vaccine). The length of time people are protected for will not be known for much longer. So far, these vaccines appear to be pushing the right buttons and we can be cautiously optimistic.

Last updated: 21 Jul 2020 12:12pm
Declared conflicts of interest:
Helen has no COVID-19 related conflicts of interest.
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-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 vaccination would reduce the symptoms of  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.

Last updated: 21 Jul 2020 10:29am
Declared conflicts of interest:
None declared.
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 COVID19.  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. 

Last updated: 21 Jul 2020 10:23am
Declared conflicts of interest:
None declared.

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