As efforts to find an effective vaccine for SARS-CoV-2 ramp up, an immunologist warns that fast-tracking of clinical trials could be catastrophic.

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A newly published commentary warns against the dangers of fast-tracking the clinical trials for finding a vaccine for SARS-CoV-2.

All data and statistics are based on publicly available data at the time of publication. Some information may be out of date.

Scientists around the globe are working to develop an effective vaccine for the novel coronavirus, SARS-CoV-2.

Until such a time, the world is reliant on physical distancing measures and personal protective equipment (PPE). Some countries are using ‘track and trace’ systems to monitor the movements of people and notify those who have been in contact with somebody diagnosed with COVID-19.

Of course, a treatment for COVID-19 is also highly desirable. Gilead’s anti-viral drug remdesivir appears to accelerate recovery time in some people. The United States and the United Kingdom have now authorized its use as a treatment for people with COVID-19.

However, as remdesivir is a treatment, not a cure, and some clinical trial results show no significant benefit, a vaccine remains preferable.

Although a COVID-19 vaccine is urgent, scientists cannot rush the development process. In a recent editorial, immunologist and deputy editor of the journal Science Advances Dr. Douglas J. Green explains why bypassing essential clinical trial stages for any such vaccine could be ‘catastrophic.’

The full comment is available to read in the journal Science Advances.

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The vaccine development process

There are currently 95 vaccines against SARS-CoV-2 in development. After the discovery and pre-clinical development stages, each of these must progress through three phases of clinical trials.

Phase I involves safety testing in a small cohort (e.g., 10–50 people). Phase II trials involve investigating the immune response in a larger cohort.

Phase III trials involve much larger groups of people (sometimes in the thousands) and must show, in a statistically significant manner, that the vaccine can protect against infection. This stage alone can take several years under normal circumstances.

In the context of the COVID-19 pandemic, this is too long to wait. Most estimates indicate that a vaccine is 12–18 months away. This is due to streamlined processes, such as accelerated pre-clinical testing and regulatory review processes.

Some experts have also advocated for ‘fast-tracking’ some clinical trial stages. They suggest that evidence that a vaccine triggers the production of neutralizing antibodies could be sufficient to progress to widespread implementation.

The article in Science Advances warns that this route could be dangerous and says scientists must conduct comprehensive safety tests for any potential vaccine.

Understanding the immune response

The article raises concerns about a repeat of the 1966 trial for a vaccine against Respiratory Syncytial Virus (RSV), which can cause serious illness in young children.

After the vaccine trial, many children still contracted the virus and suffered even worse symptoms than before. Two children died as a result.

Research conducted much later showed that the vaccine failed because it did not generate the necessary protective antibodies as the immune system had not been properly primed against the virus.

This type of immune response, which is specific to a particular pathogen, is called adaptive immunity. It contrasts with innate immunity, which is the body’s first line of defense and is not specific to a particular infection.

Adaptive immunity involves the production of specific antibodies, which is what the majority of vaccines aim to achieve.

It involves a type of immune cell called helper T cells, also known as CD4+ cells. The immune system requires these cells to produce strongly binding antibodies. This occurs through a process called antibody affinity maturation.

In the failed RSV vaccine, there was a lack of antibody affinity maturation, which caused the children to have a worse response than usual when they contracted the virus.

Studies of immune responses to SARS-COV-2 have found that the numbers of CD4+ T cells are crucial for overcoming the disease, which is a vital consideration for vaccine development.

Antibody-dependent enhancement

The failure of the RSV vaccine highlights the importance of fully understanding the immune response before progressing to clinical trials.

Another way a vaccine can cause harm is through antibody-dependent enhancement (ADE). This means that antibodies produced against the virus also bind to receptors on host cells, which ultimately means that the virus is more likely to infect them.

Experts have observed this effect in vaccines against Dengue, Ebola, and HIV, and in a coronavirus in cats.

However, several studies of SARS-CoV vaccines in rhesus monkeys – a much closer relation to humans – have shown no evidence of ADE.

Slow is fast

As well as the scientific roadblocks, there are many ethical hurdles to overcome before performing studies of experimental vaccines in people; studies that may pose significant risks. Dr. Green says that scientists must way up these “extreme risks” against the potential benefits.

The take-home message of the article is that while time is of the essence, it is essential to ensure the safety of any potential vaccine.

It is vital to ensure the safety of any vaccine, including a full investigation of its potential adverse effects. Rushing this process could have catastrophic consequences, says Dr. Green, who recommends the application of the axiom ‘Fast is slow, and slow is fast’ to COVID-19 vaccine development.

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