Posted by Care Ana, Thursday, 25th June 2020 @ 3:48pm
A new trial has begun in Victoria this week to evaluate a potential vaccine against COVID-19.
The vaccine is called NVX-CoV2373 and is from a US biotech company, Novavax.
The trial will be carried out across Melbourne and Brisbane, and is the first human trial of a vaccine specifically for COVID-19 to take place in Australia.
This vaccine is actually based on a vaccine that was already in development for influenza. But how might it work against SARS-CoV-2, the coronavirus that causes COVID-19?
What’s in the mix?
Vaccines trigger an immune response by introducing the cells of our immune system to a virus in a safe way, without any exposure to the pathogen itself.
All vaccines have to do two things. The first is make our immune cells bind to and “eat up” the vaccine. The second is to activate these immune cells so they’re prepared to fight the current and any subsequent threats from the virus in question.
We often add molecules called adjuvants to vaccines to deliver a danger signal to the immune system, activate immune cells and trigger a strong immune response.
The Novavax vaccine is what we call a “subunit” vaccine because, instead of delivering the whole virus, it delivers only part of it. The element of SARS-CoV-2 in this vaccine is the spike protein, which is found on the surface of the virus.
By targeting a particular protein, a subunit vaccine is a great way to focus the immune response.
However, protein by itself is not very good at binding to and activating the cells of our immune system. Proteins are generally soluble, which doesn’t appeal to immune cells. They like something they can chew on.
So instead of soluble protein, Novavax has assembled the SARS-CoV-2 spike protein into very small particles, called nanoparticles. To immune cells, these nanoparticles look like little viruses, so immune cells can bind to these pre-packaged chunks of protein, rapidly engulfing them and becoming activated.
The Novavax vaccine also contains an adjuvant called Matrix-M. While the nanoparticles deliver a modest danger signal, Matrix-M can be added to deliver a much stronger danger signal and really wake up the immune system.
Rethinking an influenza vaccine
The Novavax vaccine for SARS-CoV-2 is based on a vaccine the company was already developing for influenza, called NanoFlu.
The NanoFlu vaccine contains similar parts – nanoparticles with the Matrix-M adjuvant. But it uses a different protein in the nanoparticle (hemagglutinin, which is on the outside of the influenza virus).
In October last year, Novavax started testing NanoFlu in a phase III clinical trial, the last level of clinical testing before a vaccine can be licensed. This trial had 2,650 volunteers and researchers were comparing whether NanoFlu performed as well as Fluzone, a standard influenza vaccine.
An important feature of this trial is participants were over the age of 65. Older people tend to have poorer responses to vaccines, because immune cells become more difficult to activate as we age.
This trial is ongoing, with volunteers to be followed until the end of the year. However, early results suggest NanoFlu can generate significantly higher levels of antibodies than Fluzone – even given the older people in the trial.
Antibodies are small proteins made by our immune cells which bind strongly to viruses and can stop them from infecting cells in the nose and lungs. So increased antibodies with NanoFlu should result in lower rates of infection with influenza.
These results were similar to those released after the phase I trial of NanoFlu, and suggest NanoFlu would be the superior vaccine for influenza.
So the big question is – will the same strategy work for SARS-CoV-2?
The Australian clinical trial
The new phase I/II trial will enrol around 131 healthy volunteers aged between 18 and 59 to assess the vaccine’s safety and measure how it affects the body’s immune response.
Some volunteers will not receive the vaccine, as a placebo control. The rest will receive the vaccine, in a few different forms.
The trial will test two doses of protein nanoparticles – a low (5 microgram) or a high (25 microgram) dose. Both doses will be delivered with Matrix-M adjuvant but the higher dose will also be tested without Matrix-M.
All groups will receive two shots of the vaccine 21 days apart, except one group that will just get one shot.
This design enables researchers to ask four important questions:
can the vaccine induce an immune response?
if so, what dose of nanoparticle is best?
do you need adjuvant or are nanoparticles enough?
do you need two shots or is one enough?
While it’s not yet clear how the vaccine will perform for SARS-CoV-2, Novavax has reported it generated strong immune responses in animals.
And we know NanoFlu performed well and had a good safety profile for influenza. NanoFlu also seemed to work well in older adults, which would be essential for a vaccine for COVID-19.
We eagerly await the first set of results, expected in a couple of months – an impressive turnaround time for a clinical trial. If this initial study is successful, the phase II portion of the trial will begin, with more participants.
The Novavax vaccine joins at least nine other vaccine candidates for SARS-CoV-2 currently in clinical testing around the world.
Posted by Care Ana, Thursday, 25th June 2020 @ 3:46pm
Saliva is one of our biggest foes in the COVID-19 pandemic, because of its role in spreading the virus. But it could be our friend too, because it potentially offers a way to diagnose the disease without using invasive nasal swabs.
Our research review, published in the journal Diagnostics, suggests saliva could offer a readily accessible diagnostic tool for detecting the presence of SARS-CoV-2, the virus that causes COVID-19, and might even be able to reveal whether someone’s immune system has already encountered it.
COVID-19 testing is a crucial part of the pandemic response, especially now countries are gradually lifting social distancing restrictions. This requires widespread, early, accurate and sensitive diagnosis of infected people, both with and without symptoms.
Our review looked at the results of three different studies, in Hong Kong, the nearby Chinese mainland city of Shenzhen, and Italy. All three studies found SARS-CoV-2 is indeed present in the saliva of COVID-19 patients (at rates of 87%, 91.6%, and 100% of patients, respectively). This suggests saliva is a potentially very useful source of specimens for detecting the virus.
Saliva spreads the SARS-CoV-2 virus via breathing, coughing, sneezing, and conversation, which is why guidelines suggest we maintain a distance of at least 1.5 metres from one another. We also know SARS-CoV-2 can survive in tiny droplets of saliva in an experimental setting.
Saliva is an attractive option for detecting SARS-CoV-2, compared with the current tests which involve taking swabs of mucus from the upper respiratory tract. Saliva is easy to access, which potentially makes the tests cheaper and less invasive. Saliva can hold up a mirror to our health, not just of our mouth but our whole body.
For this reason, saliva has already been widely investigated as a diagnostic tool for chronic systemic diseases, as well as for oral ailments such as periodontal disease and oral cancers. But less attention has been given to its potential usefulness in acute infectious diseases such as COVID-19, perhaps because researchers and clinicians don’t yet appreciate its full potential.
What a mouthful
When we get sick, much of the evidence is present in our saliva – from the germs themselves, to the antibodies and immune system proteins we use to fight them off. Saliva also contains genetic material and other cellular components of pathogens after we have broken them down (for the full biochemical breakdown of the weird and wonderful things in our saliva, see pages 51-61 of our ).
Saliva is also hardy. It can be stored at –80℃ for several years with little degradation.
This means it would be relatively straightforward to track the progression of COVID-19 in individual patients, by collecting saliva at various times during the disease and recovery. Saliva tests from recovered patients could also tell us if they have encountered the disease for a second time, and how strong their immune response is.
However, there is no research yet available on using saliva to monitor immune responses. This will be well worth investigating, given the pressing need for a reliable and cost-effective way to monitor the population for immunity to COVID-19 as the outbreak continues.
Could saliva testing replace nasal swabs?
An ideal saliva test would be a disposable, off-the-shelf device that could be used at home by individuals, without exposing them or others to the risk of visiting a clinic.
One drawback with the research so far is that it has involved small numbers of patients (each of the three studies we reviewed involved no more than 25 people), and there is little published detail on exactly how these studies collected the saliva – whether from the mouth or throat, whether by spitting, drooling or swabbing, and whether collected by the patient or by a clinician.
Nevertheless, based on the modest amount of research done so far, saliva looks like a promising candidate for COVID-19 testing. More research is now needed, in larger groups of people, to learn more about how to COVID-19 Antibody Testfor SARS-CoV-2 in the saliva of both symptomatic and non-symptomatic people.
Posted by Care Ana, Thursday, 25th June 2020 @ 3:44pm
SARS-CoV-2, the virus that causes COVID-19, is changing how we live. With a rapid increase in cases, we are now isolating in our homes to “flatten the curve”.
However, it will be nearly impossible to eradicate the virus simultaneously all around the world. And when we do emerge from isolation, the virus could potentially re-establish itself.
Our best chance to keep it in check in the future will be to develop a vaccine.
Australia’s CSIRO has just begun testing two new vaccine candidates. These are just two of many potential vaccines that scientists are working on around the world.
Vaccine design basics
All vaccines must contain two components:
the adjuvant, a molecule that acts as a “danger signal” to activate your immune system
the antigen, a unique molecule that acts as a “target” for the immune response to the virus.
The adjuvant must be mixed with the antigen to activate an immune response. But you can’t induce any old immune response – you must trigger the right type of response for the infection you’re targeting.
Researchers divide immune responses broadly into those that make:
antibodies, which bind to the surface of viruses to prevent infection of cells
T cells, which kill cells that have become infected with the virus.
Adjuvants and antigens are selected to induce antibody and/or T cell responses to ensure we have the right kind of immune response against the right target.
The ideal vaccine would be safe, easy to administer, simple and cheap to manufacture, and provide long-term protection against COVID-19. This protection would, hopefully, completely prevent infection with SARS-CoV-2.
But, to begin with, we’d even be happy with a vaccine that could reduce the amount of virus generated during a typical infection. If an infected person is making less virus, they are less likely to infect others. Less virus could also reduce the amount of damage caused by an infection in the patient.
Know your enemy
To design an effective vaccine for SARS-CoV-2, we need to understand the virus.
The genetic sequence of SARS-CoV-2 is very similar to two other coronaviruses – 79% identical to the original SARS (severe acute respiratory syndrome) from 2003, and around 50% identical to MERS (Middle East respiratory syndrome) from 2012.
Researchers working on SARS and MERS vaccines are now providing critical basic information on vaccines that may work for SARS-CoV-2.
Other researchers working on viral vaccines for dengue, Zika, hepatitis C, HIV and influenza are also pivoting to use their knowledge for SARS-CoV-2.
The SARS-CoV-2 virus uses ribonucleic acid (RNA) as its genetic material. This is usually associated with high mutation rates, which can be a problem for vaccines, as viruses can mutate their antigens to evade the immune response. Fortunately, SARS-CoV-2 seems to have a moderate rate of mutation to date, meaning it should be susceptible to a vaccine.
The SARS-CoV-2 viral particle is covered by “spike” proteins. This spike protein binds to a molecule on the surface of lung cells called the human angiotensin-converting enzyme 2 (ACE2).
There’s a lot of spike protein on the outside of the virus, making it a prime target for our immune response. So most researchers have focused on the spike protein as an antigen for SARS-CoV-2.
There’s a lot we still don’t know
Importantly, for SARS-CoV-2 vaccines, we don’t yet know what type of immune response is needed.
We know patients who recover from COVID-19 can produce antibodies, but we don’t know what kind of antibodies.
We know COVID-19 patients who develop severe disease have low numbers of T cells, but we don’t have clear evidence of whether T cells can protect against COVID-19.
We know some experimental vaccine designs for MERS and SARS can make disease symptoms worse in animals, but we don’t know whether this would happen with SARS-CoV-2.
Since there are still a lot of unknowns, we have to cover all bases. Fortunately, dozens of vaccine designs are now advancing towards clinical testing.
Vaccines in the pipeline
Vaccine development during a pandemic happens at a global scale and is underway in several countries, including Australia.
The first vaccine to make it into clinical trials in mid-March is a lipid-encapsulated mRNA vaccine. For this vaccine, a short piece of the genetic material from the virus (mRNA) is coated with an oily layer (lipid).
The lipid helps the mRNA get inside a person’s muscle cells, and the mRNA provides a blueprint to make the spike protein the antigen (target). The mRNA itself acts as an adjuvant (danger signal).
This vaccine is now being given to volunteers in a phase I clinical trial in Seattle.
The main advantage of this vaccine is that it can be manufactured very quickly. The DNA sequence of SARS-CoV-2 used to design this vaccine was first published in January and the vaccine was ready for trials in mid-March, which is an incredibly tight turnaround for a vaccine.
But this type of vaccine has not been widely used in humans and we don’t know if it will induce robust immune responses. While modest immunity would be better than no immunity, we may need additional, more potent vaccines in the longer term.
Another type of vaccine researchers are exploring is called a subunit vaccine. In a subunit vaccine, the spike protein is used as the antigen (target), mixed with an adjuvant (danger signal) to activate the immune system. The shape of the spike protein must be highly consistent to generate a robust immune response.
A team at the University of Queensland is using a “molecular clamp”, which is a short piece of protein that holds a larger protein in the correct shape. They are working together with CSIRO, which is now producing large quantities of this clamped antigen and is beginning testing of this and other vaccines.
There are also newer approaches, such as “viral vector” vaccines. Scientists make a viral vector by taking genetic material from SARS-CoV-2 and inserting it into a harmless virus. When this is given to a person, the docile viral vector can’t cause any disease but it looks like a vicious virus to the immune system, and so it can generate robust immune responses.
These vaccines were rolled out rapidly for the Ebola epidemic in West Africa in 2014 and in Congo in 2018/19 with promising results.
They’re on their way for SARS-CoV-2, with CSIRO beginning to test a viral vector called ChAdOx1.
Readmore: COVID-19 Antibody Test