Cambridge (UK), Sept 1: (The Conversation) SARS-CoV-2, the virus responsible for COVID-19, has turned the world upside down. Experts have predicted that it will claim the lives of between 9-18 million worldwide. This is in addition to destroying the livelihoods, mental health and education of countless others. The pandemic will probably wreak havoc for many years to come, despite the remarkable speed of vaccine development. This is not helped by the emergence of new variants sweeping the world, which pose a serious threat to the success of vaccination and upcoming treatments.
It is difficult to predict the future pattern of SARS-CoV-2. Many scientists believe it will continue to circulate in pockets around the globe, meaning that it will become endemic in the same way as flu. In this context the number of infections remains relatively constant with occasional flare-ups that run the danger of turning into a pandemic. A lot depends on how widely the population around the world can be vaccinated and how long immunity lasts after natural infection or vaccination.
Long term, the best solution would be to develop a universal vaccine – one that would help protect against all current variants of the coronavirus and any others that arise in the future. Without it, the world runs the risk of recurrent pandemics.
Given the difficulties encountered in creating a universal flu vaccine, this may seem a tall order. But a number of scientists believe it is possible based on the rapid development of the SARS-CoV-2 vaccines.
COVID-19 is in fact the third major infectious disease outbreak to have been triggered in the last two decades by a new coronavirus jumping from animals into humans, the other two being Sars and Mers.
To get a sense of how far a pan-coronavirus vaccine has progressed we spoke to a number of key players in the field. We are both experts in this area but come at it from very different angles – Lara Marks is a historian of medicine with an interest in biotechnology and vaccines, while Ankur Mutreja has experience in tracking outbreaks and developing vaccines for infectious diseases. From our conversations, there appear to be a number of encouraging vaccine candidates on the horizon – it is even possible that one could be developed for use in humans within 12 months.
‘The holy grail’
One of the first people we spoke to was Richard Hatchett, the CEO of the Coalition for Epidemic Preparedness Innovations (Cepi). Set up in 2017, Cepi is a global partnership between public, private, philanthropic and civil society organisations that aims to compress the development of vaccines against emerging infectious diseases into 100 days – a third of the time achieved with the first COVID-19 vaccines.
Envisaging equitable access to vaccines for all countries, in March 2021, Cepi announced it would raise and invest US$3.5 billion in vaccine research and development to strengthen global preparedness to pandemics, of which US$200 million has been put aside to develop a universal coronavirus vaccine. Such a vaccine would offer protection against a broad range of coronaviruses, regardless of their variants. This would reduce the need to modify the vaccine on a regular basis.
Hatchett described these vaccines as the “holy grail”. But he argued it may take years of investment. He said: “If you want to grow a tree, the best thing to have done is to have planted it 20 years ago. And if you didn’t do that, then the next best thing is to plant it today.”
When asked about what the best vaccine would be going forward to deal with SARS-CoV-2, Hatchett replied:
We do not actually know specifically yet. This is really our first engagement with this virus, obviously, and we’ve watched it expand and unfold over time … We’re still gathering data and gaining experience on this. I think we need to have some humility about what we know currently and what we can know. We just have to be vigilant.
Why is SARS-CoV-2 mutating?
None of the scientists we interviewed were surprised to see SARS-CoV-2 mutating. All viruses mutate. They often undergo random genetic changes because the virus replication machinery is not perfect. It is a bit like a game of “telephone” where children repeat what they thought they heard, making mistakes all along the way so that the final message is very different from the original one. Whenever a virus develops one or more mutations it is considered a “variant” of the original virus.
The mutation process helps viruses to adapt and survive any onslaught from the host’s immune system, vaccination or drug treatment and natural competition. Viruses change faster when under such pressures.
Scientists have been monitoring the genetic variations in SARS-CoV-2 since the start of the pandemic. They do this by sequencing the total RNA (genome) of the virus collected from patient samples. The genome is the complete set of genetic instructions an organism needs to function and thrive.
Scientists in China managed to sequence the first SARS-CoV-2 genome just one week after the first patient was hospitalised with unusual pneumonia in Wuhan. First drafted on January 5 2020, the sequence revealed the virus to be a close relative of SARS-CoV-1, a human coronavirus which caused an outbreak of a severe respiratory disease SARS that first appeared in China in 2002 and then spread to many other countries. It also resembled a SARS-like coronavirus found in bats.
Comprising a single-strand of RNA, the SARS-CoV-2 genome turned out to be the longest genome of any known RNA virus. With the aid of sequencing scientists were quickly able to pinpoint the genes that carry the instructions for the spike protein, the part of the virus that helps it to invade human cells. This became an important target for the development of COVID-19 vaccine.
Initial genome sequencing data suggested that SARS-CoV-2 mutated much slower than most other RNA viruses, being half the rate of the virus responsible for flu and a quarter of that found for HIV. But its mutation rate has gathered speed over time, helped by the large reservoir of people it has infected and selection pressures.
Not all mutations are bad news. In some cases, they weaken the virus with the variant disappearing without a trace. But in other cases, they enable the virus to enter a host’s cells more easily or to escape the immune system more effectively, making it more difficult to prevent and treat.
So far, five new variants of concern have emerged with SARS-CoV-2. The first (alpha) was detected in south-east England in September 2020. Others were found shortly thereafter in South Africa (beta), Brazil (gamma), India (delta) and Peru (lambda).
What is troubling about these new variants is that they are more transmissible, making them spread faster, which increases the likelihood of re-infection and a resurgence in cases. Every SARS-CoV-2 virus out there today is a variation of the original and new variants will continue to appear.
Preliminary research suggests that the first-generation of vaccines offer some protection against the new variants, helping to reduce severe disease and hospitalisation. However, they will probably become less effective over time as the virus mutates further and the immunity that people have gained, either through vaccination or natural infection, wanes.
Looking for weak spots
In terms of a universal coronavirus vaccine, the ultimate question, Hatchett believes, is whether there are any weak spots that are “conserved across coronaviruses as a viral family to which you can develop immune responses that effectively protect you”.
The key issue in creating a universal vaccine is how broad a coverage the vaccine should offer. This was also pointed out to us by Andrew Ward at the Scripps Research Institute in California. As he put it:
Should it be SARS-CoV-2 and variants? Should it be SARS-1 and SARS-2? Should it be all sarbecocoviruses [a subgroup of SARS viruses of which SARS-CoV-1 and 2 are notable members] or SARS-like viruses? That’s unknown. We know that SARS viruses exist in bats and pangolins and they’ve never been as big of a problem as now. But it’s one of those things, that if it’s not really a problem do we go after it and try to proactively get vaccine programmes deployed and get people either vaccinated or stockpile vaccines?
Creating a universal vaccine is itself highly challenging. For example, scientists have tried for years but not yet succeeded in developing a universal vaccine for flu. Nor have they yet managed to create one for HIV. In part, this is because the surface proteins found on these viruses frequently change their appearance. This makes it difficult for our immune system to recognise the virus.
But scientists have made enormous advances in recent years in understanding the interaction between the immune system and viruses that cause flu and HIV. They are now deploying this knowledge to build a universal vaccine for coronaviruses, which do not change as fast.
A long history of vaccine innovation
One of the reasons for optimism with a universal coronavirus vaccine is the successful development of the SARS-CoV-2 vaccine. Made in record time, the foundation for the vaccine was laid many years ago. Until the 1980s most vaccines were developed by modifying a virus or bacteria to make it no longer dangerous.
This was achieved by weakening or inactivating the pathogen so that it could be injected safely to stimulate an immune response. While highly successful for protecting against a host diseases like measles, polio, rabies and chickenpox, this approach didn’t prove effective in all diseases.
(AGENCIES)
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