We all know it - the only way to completely defeat the novel coronavirus is by developing a vaccine against it. While social distancing measures and lockdowns can help delay its spread, only immunisation through a vaccine can halt it altogether.
But vaccines take time. A host of steps are involved before a candidate reaches the public: research, safety testing, preclinical and clinical trials, licensing, mass production and dissemination. You can read about the stages here.
The fastest ever vaccine to be developed is the one for mumps - and even that took four years.
In these unprecedented times, when the SARS-CoV-2 (the novel coronavirus) is taking thousands of lives every single day, can the world afford to wait? This question centres the debate over ‘human challenge trials’ - trials which can accelerate vaccine development, but which also evoke significant ethical dilemmas. What do they entail and why are they controversial? FIT explains.
What Are Human Challenge Trials?
A vaccine needs to be tested for safety and efficacy. In the later stages of clinical trials (phase III), when the safety has been established, researchers typically divide thousands of human volunteers into two groups - administering the vaccine to one and giving a placebo to the other.
After this, they wait.
Whether the vaccine worked or not is only known if and when the volunteers get exposed to the virus during the course of their daily lives, which is followed by a comparison between the two groups to see if the vaccinated individuals were protected. This can take weeks, months, or even years, especially when people are consciously following precautions and social distancing measures to avoid getting the infection.
A human challenge trial fast-tracks this process by deliberately infecting these individuals with the virus, that is, ‘challenging’ their bodies to fight the pathogen.
The hypothesis that vaccinated individuals would have developed immunity against the virus can then be tested sooner.
These trials have been conducted for influenza, malaria, typhoid, cholera and shigella, among other diseases. Speaking to FIT, Dr Shahid Jameel, a Virologist & CEO of Wellcome Trust DBT India Alliance, said, “For most illnesses where these trials have been used, there are drugs available to beat the disease, like in malaria. That is where COVID-19 is different.”
Conducting challenge trials for a five-month-old disease with no known cure, drug or treatment, elicits the question: How ethical is it to intentionally infect healthy people with the virus?
Dr Neha Gupta, Consultant, Infectious Disease at Fortis, Gurugram, tells FIT, “The need to develop a safe and efficient vaccine is of paramount importance today. It’s an urgent health priority.”
The Ethical Dilemma; What Experts Think
Dr Jameel feels that even though the trials can fasten vaccine development and save crucial time, opting for them in the case of this disease is ‘fraught with a lot of ethical issues’ because so far, there is no drug that works.
FIT spoke to Dr Om Shrivastav, Director, Infectious Specialist Diseases at Jaslok Hospital, who said,
A team of researchers at Rutgers University in New Jersey has actively advocated these studies for COVID-19, by challenging volunteers with the live virus while also laying down ways to ensure the safety and ethicality of the experiments. “We argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity.”
The study, published in The Journal of Infectious Diseases, argues that by enrolling only healthy young adults, who are at relatively low risk of disease following natural infection and have a high baseline risk of infection, the net risk could be minimised to the least. These people would be frequently monitored, and following any infection, would receive the best available care.
Replacing Phase III trials which involve thousands of volunteers with human challenge trials would not only accelerate the process, but also bring down the number of individuals needed.
Nir Eyal, the director of the Center for Population-Level Bioethics at Rutgers University in New Brunswick, New Jersey, and lead author of the preprint, tells Nature, “The dramatic-sounding exposure of healthy volunteers to the virus is, therefore, adding less net risk than you might think. It might even be curiously safer for some to join the study than to await probable infection and then try to rely on the general health-care system.
Christine Grady, chief of the department of bioethics at the NIH clinical centre, was a bit more sceptical in a conversation with Stat News, “We don’t yet know why some people get sick and others don’t or why some people get certain manifestations of COVID-19 that others don’t get. There’s so much emerging information about this sort of clinical course of infection and also susceptibility to infection that it makes an assessment that it’s OK to subject a certain age group to risk a little bit too fast for me.”
“I wouldn’t take it off the table, but I certainly wouldn’t say we’re ready for it now. And I certainly wouldn’t let it divert activity from other ways of testing vaccines”, he said.
Over 10,000 Human Volunteers Willing to Take Part; Where Does the World Stand?
In a working document released by the World Health Organisation on 6 May, titled ‘Key criteria for the ethical acceptability of COVID-19 human challenge’, eight criteria were listed to consider the trials.
Josh Morrison, a 34-year-old man in the US who is an active advocate for kidney donors, started a group called ‘1DaySooner’ to organise volunteers who would be willing to take part in challenge studies for COVID-19. More than 16,000 people have signed up across 102 countries.
While there are no assured public plans for any such trials, several politicians and experts are pushing for one. London-based hVIVO and Switzerland-based SGS are also working to launch these studies, reported NBC News. Even the Food and Drug Administration (FDA), which has never allowed such a trial for a novel disease without a cure, is not ruling it out. In a statement, it said,
Dr Matthew Memoli, director of clinical studies at the Laboratory of Infectious Diseases at the National Institutes of Health, reportedly said that it’s likely the world sees one such trial at some point in the future, “I definitely think it's going to be pursued.”
Even politicians have shown interest in the trials, with 35 House members in the US urging regulators to consider the studies, an NBC report mentions.
Notably, these trials had been rejected for Zika virus in 2016, but experts assert that this was because of the risk involved for non-participants, like sexual partners of the volunteers. In the model suggested by Nir Eyal’s team, for instance, the study participants are isolated to diminish the risk for everybody, he said in his interview with Nature.
Decisions regarding experiments that could potentially risk lives, however, would always have to be evaluated with utmost scrutiny.
"When I think of a human challenge model, I think, 'Can I get this information any other way?'" Dr Beth Kirkpatrick, chair of microbiology and molecular genetics and head of the vaccine testing centre at the University of Vermont, told NBC. "If we can find another way to do it, often we don't go this way,
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