Infecting people with COVID-19 could speed vaccine trials. Is it worth it? – Science News

The world waits with bated breath for a COVID-19 vaccine, which could effectively end the pandemic once its widely available. Until then, more people will die from the disease, and economies will struggle to fully recover.

With such intense pressureto get a vaccine quickly, many experts are contemplating a controversial shortcutto the usual vaccine testing protocol: human challenge trials.

Instead of vaccinatinghundreds to thousands of people and waiting to see if they naturally catch thevirus, scientists would purposely infect a smaller number of vaccinated volunteerswith COVID-19 in a controlled setting to see if a vaccine offered protection.If successful, such studies could fast-track vaccine evaluation, as well as ourunderstanding of COVID-19 immunity.

However, doctors andresearchers dont all agree on whether its ethical to infect people with adisease that remains poorly understood, and for which there is currently noreliable treatment. That leaves it to those bioethicists, researchers andregulators to weigh the pros and cons.

If scientists stick to theusual playbook, a licensed vaccine is at least 12 to 18 months away, expertssay. Thats not because it takes long to develop possible vaccines dozens are already in the testing stage (SN: 5/20/20) but because of the time that ittakes to be sure a vaccine is safe and actually works.

The final and most involvedstage of this process, Phase III clinical trials, requires thousands of volunteersto get the vaccine or a placebo. Then, scientists track them over months to seewhether vaccinated people are less likely to get sick compared withunvaccinated people.

And it could take longer nowthat lockdowns and social distancing have flattened the curve of new cases.You can only test vaccine efficacy if incidence [of the disease] is highenough, says Helen McShane, a vaccine biologist at the University of Oxford.The less the disease is spreading, the longer traditional Phase III trials willtake.

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Challenge trials might shavemonths off the process. Human challenge trials have been done for hundreds ofyears, says Seema Shah, a bioethicist at Northwestern University MedicalSchool in Chicago. They come with a lot of promise, but also with seriousethical concerns.

For example, in 1796, Englishphysician Edward Jenner, an earlier popularizer of vaccination, demonstratedthat inoculation with cowpox worked as a vaccine against smallpox by injectinghis gardeners 8-year-old son with cowpox and then exposing him to the disease.Clearly, thats problematic, Shah says.

Nowadays, challenge trialsare typically done on diseases about which scientists know a lot, and for whichthere are numerous treatment options, such as influenza or malaria. But therescurrently no established drug safety net for COVID-19, though some drugs show promise (SN: 4/29/20).And much still remains unknown about the virus, including all the risk factors for severe disease (SN: 4/22/20).Consequently, most advocates are calling for such trials to be done only onyoung and healthy volunteers, who seem least at risk for serious illness.

Still, researchers,clinicians, bioethicists and policymakers are debating the ultimate utility ofhuman challenge trials for COVID-19. The ethical calculus could change as welearn more about the virus and continue developing treatments, but some expertsare already putting out rough plans for how to minimize risk to participants.

Here are two perspectives onthe issue, from scientists weighing both the risks and potential benefits.

We face a worldwideepidemic with a high mortality, and the only thing likely to stop it is vaccination,says Stanley Plotkin, a vaccine developer at the University of Pennsylvania.Human challenge trials have the potential to get us an effective vaccine soonerand thus save lives, Plotkin says, and we should start planning how to do themethically now.

I would, of course, notwant to subject anyone to harm, but the fact is that harm is accumulating allover now, and if we can reduce the total amount of harm, I think its worthdoing, Plotkin says. Extraordinary circumstances require extraordinary solutions.

Human challenge trials couldhelp scientists answer important unknowns about the virus more quickly thananimal studies can, Plotkin says. A human challenge trial could tell uswhether prior infection is protective or not, as well as what sort of immuneresponses are protective, Plotkin says. Both of those have very largeimplications in terms of whether people with prior infection could take care ofthe sick, as well as our ability to evaluate the efficacy of vaccine candidatesoutside of challenge trials.

Plotkin acknowledges thepotential risks to participants. Giving someone an infection can cause seriousharm, he says, but the usual way of doing things also means that many peoplewill become ill and possibly die. To minimize risk, Plotkin says such trialsshould only be carried out on young, healthy people who understand the risksand give their full consent. There are thousands of people willing to bevolunteers for such studies on moral grounds, with knowledge of the risks.

A vaccine shown to work in achallenge trial on young people may not work in older people, or may be lesseffective, Plotkin says. But a challenge trial could allow us to more easilydetermine whether the immune responses we see in younger people are also seenin older people, who get the experimental vaccine but arent subjected to achallenge virus. Even if the vaccine only worked in younger folks, that couldstill protect older people simply because they wouldnt be getting infected byyounger [vaccinated] people, he says.

While some have argued that challenge trials could replace Phase IIIclinical trials, Plotkin doesnt seehuman challenge trials as a full substitute for normal safety trials. He also doesntexpect them to result in regulators licensing a vaccine for widespread use.But it could allow for emergency use among high-risk people or health careworkers, he says. It could also help us determine which vaccine candidatesshow signs of working, which could allow manufacturers to get a potentiallylifesaving head start on mass production.

This is not an exclusivepathway, he says, its a supplementary pathway to try to speed things up. Ifnormal vaccine trials revealed a candidate, or we learn more about the risks tovolunteers, Plotkin says challenge trials should be stopped. But if we dontstart planning human challenges now, they wont be available if we decidemonths from now that it wouldve been a good idea.

I still havent beenpersuaded that a human challenge trial would be informative enough to make afinal decision about which vaccine is the right vaccine to roll out at scale,says Angela Rasmussen, a virologist at Columbia University.

The hallmark of any humanchallenge trial is fully informed consent from participants. But Rasmussenquestions whether thats possible at this stage. I dont know that we canactually inform them of all the risks because theres still so much thats justunknown about this virus, she says.

Evidence suggests thatyoung, healthy people are least likely to suffer severely from COVID-19infection, but were still learning about different types of disease that itmay cause, Rasmussen says. Reports of young people suffering strokes, andtaking damage to the kidneys, heart and other organs have emerged in recentmonths, making it difficult to quantify the actual risks. I just dont see howa subject could provide their fully informed consent.

Accepting those risks may resultin more harm than good, Rasmussen says. By design, any COVID-19 challenge trialwould be done on a small, homogenous group. That could limit its broaderapplicability, she says, and could miss issues with the vaccine that can onlybe caught in a larger, more diverse study population.

She points to previousexamples, like the mid-2000s HIV vaccine candidate that actually increased risk of HIV infection in those who got the vaccine, or a SARS classicstudy in which older vaccinated mice experiencedmore severe disease after beinginfected.

My concern is that youcould have a major safety issue like that if you are doing only human challengetrials in young, healthy volunteers, Rasmussen says. A robust response inyoung people could mask harmful effects that emerge in older people or adifferent population, she says.

While a challenge trialcould identify promising vaccine candidates more quickly, it might also prop upthe wrong one based on limited results. If serious issues come up for otherpopulations, the consequences could be dire, Rasmussen says. And wed have wastedresources that could have been devoted to standard Phase II and III trials.

Other unknowns limit achallenge trials potential utility, too, Rasmussen says. We dont know theinfectious dose for COVID-19, she says, meaning the amount of virus that someonemust get to kick-start an infection. If a challenge trial got the dose or routeof infection wrong, it might not be comparable to pathogenic SARS-CoV-2, thevirus that causes COVID-19. A vaccine would appear to work under thoseconditions, but it might not be applicable to how people actually need to beprotected in the real world.

Rasmussen doesnt rule outthat challenge trials could be helpful. Its important to keep an open mindabout anything that can speed our way to a vaccine, but we need to be cautiousand be humble, Rasmussen says. Theres a lot more we dont know about thisvirus than what we do know. If a human challenge trial goes wrong, it could gocatastrophically wrong, which could ultimately be harmful for all vaccinedevelopment efforts.

Exactly who gives the green light for a COVID-19challenge trial remains unclear. Normally the decision to proceed with such a triallies with the funder of the research (the U.S. National Institutes of Health,for example) and ethics boards at the research institutions or regions wherethe study will be done.

But given the extraordinary nature of the currentsituation, the World Health Organization, as well as leaders of the NIH, have called for an additional layer of review for anyCOVID-19 challenge trials, which could include an independent panel ofethicists, clinical trial researchers and vaccine development experts.

In the United States, the Food and DrugAdministration would license a vaccine for widespread use, and they would haveto decide whether results of a human challenge study would weigh on theirultimate decision. Its not a given that the agency would take those resultsinto consideration.

Meanwhile, people are already volunteering to take part in COVID-19 human challenge trials, were they to happen. Already, over 20,000 people around the world have expressed interest in participating in COVID-19 challenge trials through 1 Day Sooner, a campaign to collect volunteers.

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Infecting people with COVID-19 could speed vaccine trials. Is it worth it? - Science News