Exploring Coronavirus Vaccines-Dangerous and Uncertain Road | World News

THis stakes will never get higher. The prizes are not yet appetizing. It’s no exaggeration to say that the fate of millions of people depends on the discovery of the Covid-19 vaccine. This is the only sure escape route from a pandemic.

But the optimism associated with the start of this week’s Oxford University trial of humans needs to be put in the background and the hurdles scientists face.

Vaccine hunters can hold 1 million virus particles inside human cells in order to make invisible enemies unnoticeable, but their biological device halts daily life.

So what is the path to success?

How Vaccines Train the Immune System

Traditional vaccines work by creating a version of the virus that is as weak as the original one, and in the future, when a person is exposed to a complete infection, the immune system is blocked, preventing the actual illness. Useful

This approach has yielded some of the best vaccines, but it is also fundamentally risky as the newly developed attenuated virus may not always be as harmless as one might expect. Clinical trials should be approached carefully and slowly, especially if there is no effective cure for the disease.

In a pandemic, a slow approach is not ideal.

So it’s probably not surprising. two World Health Organization lists 76 vaccine candidates To radar We chose this traditional approach.

The rest relies on the Fast Track idea that the immune system doesn’t have to see the whole virus to generate ammunition to fight it off in the future. If the virus is a warship, the theory is that the immune system only needs to see the enemy’s flag and form an indelible immune memory. In Covid-19, this flag takes the form of a prominent process called a spike protein, forming a halo or “corona” around the virus.

Advances in genetic engineering have taken a whole leap in the creativity of scientists in the development of this defense.

Teams around the world moved at an unprecedented pace, vaccinating candidates weeks after the January spike protein gene sequence.

However, many of these technologies are unproven and, like this week, no one guarantees the success of any exam. The disappointing result of the drug lem decivil show. Ethnic questions need to be navigated to ensure the safety of volunteers.

And the most controversial question of all: if a vaccine is found, who gets it first?

Front runner

First to clinical trialJust eight weeks after the Covid-19 gene sequence was published in January, the US biotechnology company Moderna, which used RNA vaccines, was born.

RNA is a single-stranded messenger molecule that normally causes genetic instructions to be rolled up into the cell from DNA and delivered to the extracellular protein production plant.

In this case, RNA tells muscle cells to make harmless spike proteins as a warning to the immune system. This week, a team of Imperial College London, backed by £ 22.5 million in government funding, is also developing an RNA vaccine, but it has never been tested in humans.

Robin Shattock, who leads the Imperial team, said: “We don’t have that luxury. It will probably take a month or two, but we recommend you go carefully and get something really safe.”

In addition, with CanSino Biologics, a vaccine company in China, Oxford University It is headed by Professor Sara Gilbert.

Both use harmless viruses, so once they enter the cell, they do not replicate. These delivery vehicles are known as “non-replicating viral vectors.”

These teams have already tried and tested approaches to other diseases such as Ebola and had a flask of vector in the freezer ready.

The third approach is US biotechnology company Inovio, Which had been around for 40 years without developing an approved product, had its inventory skyrocketed after the trial began earlier this month.

The vaccine uses DNA to carry the instructions to make cells spike proteins, which are transcribed into messenger RNAs, which in turn command the protein factory to send out enemy spike proteins.

This may seem like an unnecessarily complex cascade, but some consider it important to place the enemy’s flag inside the cell, not just in the bloodstream.

“It’s clear that no approved RNA or DNA vaccines are on the market today,” said Inovio CEO Joseph Kim. “But I think it’s a matter of time.”

Finally, the fourth strategy is to simply manufacture a large supply of spike proteins themselves and inject doses directly into people.

This is what the big pharmaceutical teams at Sanofi and GSK are betting on. Sanofi reuses vaccine candidates developed for Sarz in the early 2000s, and GSK also provides components that boost the immune response known as adjuvants.

According to Richard Hatchet, CEO of the Coalition for Epidemics (Cepi), which funds the development and testing of eight candidates, it’s time to say which option looks the most promising. It’s too early.

“Some vaccines will be very fast in the clinic, others have great potential to expand,” he said. “And the challenge we face is, for obvious reasons, the urgency and pressure to deploy vaccines quickly is huge. You talk about giving healthy people medical products. There is. “

How likely are they to work?

Some candidates are excluded in animal toxicity studies. It may also fail because of unexpected side effects in Phase 1 clinical trials.

None may work.

For some illnesses, including other circulating coronaviruses, the immune system battles that fight, forgetting that it happened a few months later. Others, such as chickenpox and mumps, cause lifelong immunity.

The truth is not yet clear where Covid-19 lies in this spectrum.

Marcus Lipsitch, a professor of epidemiology at Harvard University, recently predicted that without vaccines, there would be a partial social distance, “estimating partial protection for nearly a year,” he said. Told. May need to continue until 2022. “Maybe in the long run, it may be a good protection for years, and at this point it’s really speculative.”

On the positive side, Covid-19 appears genetically very stable. So the spike proteins that make up the vaccine should look the same next winter.

This is not the case with the flu. Influenza rapidly shuffles its genes, so new vaccines are needed every year.

There are also questions about the type of immunity needed.

The body overcomes the disease by antibodies that overlook the virus itself and killer T cells that eliminate cells already infected by the foreign invader. Antibodies become more severe in some diseases, but the balance varies by pathogen and even by person.

“An ideal vaccine should generate a response on both arms of the immune system, both antibodies and T cells,” Kim said. He predicts this could be a weakness in extracellularly delivered RNA and protein vaccines. That is, killer T cells may not be recruited.

It is possible that some trials will be stopped simply because the pandemic is very well controlled by lockdowns and other means. “We need a certain hit rate in the vaccinated population to get statistics showing that the vaccine is protective,” said Public Research Director Miles Carroll. health Portondown, National Infectious Diseases Agency in England.

While the potential for “challenge trials” to infect people intentionally has been considered, there are clear ethical issues in exposing volunteers to potentially deadly illnesses.

According to Andrew Pollard, a senior researcher at Oxford Studies, “There’s a lot of interest in this as vaccine development really accelerates, but there are some major hurdles to keeping volunteers safe in that environment.”

Scale up

Vaccine manufacturers speak in terms of yield. How many times can I get the vaccine per liter of culture? And there may be huge differences in the ability of a team to produce the number of doses needed to make a difference.

Shattock believes this is a strength of Imperial’s RNA vaccine candidate. It has the unique feature of replicating once and a thousand times in the body.

“One liter of material can make as much as one million doses,” says Shattock. “Many other vaccines require hundreds or thousands of liters for that. It’s scalability. We plan to make tens of millions of doses towards the end of the year.”

“If our vaccine proved successful, and if all went well, and still it was big, we could deploy it in the UK this winter,” Shattock said. It was. “All these small approaches hold the fort until a larger global solution is realized.”

By September, there may be widespread safe and effective vaccines (probably several).

While that is not enough to get a vaccine license, the government could already include millions of healthcare workers under the “emergency use” rule in the absence of this final approval seal. We have already discussed the possibility of expanding such a candidate to a high risk group with

This has precedent. In the 2018 Ebola outbreak, more than 200,000 people in the Democratic Republic of the Congo received the Merck vaccine before being licensed in 2019.

“If you live in an intensive care nurse or an elderly home, that may be enough. That is, you can get the most benefit from being vaccinated, so the risk-benefit balance is favorable. “Sandy Douglas says. Oxford Vaccine Researcher.

But very rare side effects cannot be ruled out. And there was a vaccine disaster in the past – recently GSK vaccine Pandemrix, Was administered to millions during the 2009 swine flu pandemic and was associated with narcolepsy at a rate of 1 in 55,000.

The principle of transparent informed consent is important, Douglas added. “In this case, if we were given a vaccine in October that didn’t exist in April, we don’t have long-term safety follow-up experience yet, but we don’t have long-term experience. With some similar vaccines . “

Individuals may face rigorous choices – be vaccinated with an vaccine or leave yourself at risk of infection.

Global solution

Many teams are currently trying every way to develop a vaccine, but there is no consistent solution across the globe. Some companies use large pharmaceutical companies that are growing fast with blockbusters. Sanofi and GSK are unique in that they can work together to produce hundreds of millions of doses without relying on external support.

However, multinationals aren’t built for speed and their reputation relies on absolute safety, so the team is likely to have widespread availability of vaccines in mid-to-late 2021. there is no.

Some people want a unified approach. Governments, the United Nations, the World Bank, and WHO need to agree on ways to move forward before a strong candidate appears.

Governments already have pre-purchase agreements and aim to secure their own supply chain.

“If vaccine nationalism claims it, you might be limiting the vaccine to one particular population,” Hatchet said. “It’s the understandable response of the leaders elected by a particular group to protect it. [But] We cannot protect people and the economy until the global pandemic is overwhelmed. We can’t deal with this one country at a time. “

Hatchet and colleagues argue for tens of billions of dollars of global effort to ensure that successful vaccines are distributed worldwide, and when needed. “From a global health perspective, that’s a huge number,” he said. “But if your reference point is the global impact this pandemic is having on the economy, it’s very few. If you agree with the idea that a vaccine is an escape path from a pandemic, it’s a really good investment. is.”