How to ensure the effectiveness of the new crown vaccine? How far is it from listing?

BEIJING, March 31 (Xinhua) — A radical proposal to conduct a “human challenge” study could significantly speed up research on the new coronary vaccine. In the context of the new corona outbreak, hundreds of millions, if not billions, of people have begun to cut off society in order to save themselves and their communities from infection. To end the pandemic as soon as possible, researchers began discussing a potentially radical way to infect a small number of healthy volunteers with the virus so that the vaccine could be tested quickly.

How to ensure the effectiveness of the new crown vaccine? How far is it from listing?

SARS-CoV-2 virus imaged by electron microscope. Source: National Institutes of Health

Many scientists believe that vaccines are the only solution to the new coronaworld. In March, researchers from different countries began clinically testing candidate vaccines, and other vaccines will soon follow suit. One of the biggest obstacles, however, is how to prove the effectiveness of the vaccine. Typically, vaccines are developed after a small-scale population trial to a large-scale trial process, after the Phase III clinical trial may not be approved for the market, when the vaccine can really be called “vaccine.” During clinical trials, tens of thousands of people receive a vaccine or a placebo, and researchers will track those infected in their daily lives.

In a recent preprinted article, the researchers offered a proposal that a faster option to end the outbreak would be to conduct a “human challenge” study. This will involve exposing about 100 healthy young people to the virus to see if vaccinators can avoid infection.

Nir Eyal is director of the Center for Bioethics at the Population Level at Rutgers University and lead author of the pre-printed paper. In an interview with nature, he described how the study should be conducted safely and ethically. He believes that participants may even benefit from it. Here are the main contents of the visit.

Why should we consider the “human challenge” study of the experimental new corona vaccine?

The main attraction of these studies is that they can significantly speed up the approval and potential application of vaccines. The longest trial of vaccines is phase III efficacy trials, which require trials on many, many people, some with the vaccine and some with a placebo or other candidate vaccine. The researchers then needed to look for differences in infection rates between the two groups.

However, many people will try to be cautious (e.g. self-isolation) during this outbreak, which will take a long time until an interpretable result is achieved. Conversely, if all study participants were exposed to pathogens, they could not only rely on fewer volunteers, but more importantly, to get results in less time.

Is there a precedent for infecting healthy people with pathogens?

We often conduct human challengestudies on non-fatal diseases such as influenza, typhoid, cholera and malaria. Exposure to deadly viruses also has some historical precedents. The difference between our proposal and some historical cases is that we feel there is a way to make these tests surprisingly safe.

How do you do such research?

Only after some initial testing can the candidate vaccine be ensured to be safe and to achieve an immune response in the human body. Then, collect a group of people who are at low risk of exposure – young and relatively healthy – and make sure they are not infected. Give them a candidate vaccine or placebo, and then wait enough time for them to have an immune response. Then expose them to the virus.

Next, closely follow all participants to detect any signs of infection as early as possible. You’ll check if the vaccinated group is better than the placebo group. The condition described here may be the level of the virus, the time the symptoms appear, or whether they are infected.

What are the risks of participants?

By choosing a relatively young (we think between the ages of 20 and 45) and a healthy experimenter, the risk of injury can be significantly reduced. You can also choose people who may have been exposed to COVID-19, either during the trial or at a later time. Unfortunately, many of us fit this description because we live in high-transmission areas of the new coronavirus.

You can also protect study participants by checking participants for infection on a daily (or more frequent) basis and providing them with excellent treatment as soon as symptoms are detected. This is not insignificant. I’ve advised intensive care doctors to be prepared for a surge in new coronavirus infections. We strongly anticipate that, based on the experience of Italy and other countries, there will be a serious shortage of critical medical resources. In parallel with the trial of a candidate vaccine, there may be some treatments that have been shown to be effective. Of course, we should make sure that these brave volunteers are ready to apply new therapies.

As a result, exposure of healthy volunteers to the virus increased the net risk less than thought. For some people, it may even be safer to participate in this study than to wait for a possible infection and then try to rely on the general health care system.

Is this moral?

On the face of it, it seems that anyone who volunteered for such a study lacks the ability to make rational decisions, or must have misunderstood the information consent form. However, humans have done many important things out of altruism. And, as I said, while this study introduces risk, it also eliminates it. While we still don’t know how big the net risk will be, it shouldn’t be particularly high. Thus, there is a potential rationality to participate in such research, even from a selfish point of view.

We’ve also been getting people to volunteer to do some risky things. During this time, for example, we have made people volunteer to be emergency medical personnel. This greatly increases their risk of infection, but it is also important. In general clinical trials, we focus not only on reducing the risk to participants; In this case, vaccines may be the only way for our societies to escape the link between economic stagnation and widespread death.

Should participants be paid?

I happen to be a bioethicist and i’m not opposed to attracting research participants by providing economic incentives. But I think it’s important to ensure a high level of public trust in this study, and I would advise researchers not to attract volunteers with high pay, which is good enough to ensure that the study is not just for the poor.

A few years ago, U.S. government donors considered a human challenge trial of a vaccine against the Zika virus, but decided to abandon it. Do you think the funders will come to a different conclusion about the coronavirus?

I think the example of the new crown vaccine is very different from the Zika vaccine. In the Zika vaccine challenge study, the objection stems in part from the risk to non-participants, primarily their sexual partners and their possible fetuses. By isolating study participants for a limited period of time, we can completely eliminate the risk of new coronavaccines to non-participants. Do I believe countries will join? Judging from the reaction of various stakeholders since the publication of this preprinted paper, I am sure many countries will do so. (Any day)