‘The Power of Natural Immunity’: COVID Challenge Trials Struggle to Infect Participants, Even at High Doses

U.K. scientists attempting to deliberately reinfect healthy people with COVID-19 for vaccine and treatment testing found that even doses 10,000 times higher than the original could not induce sustained infection in participants with natural immunity from prior infection, as reported in The Lancet Microbe.

Scientists trying to reinfect people with the COVID-19 virus so they could test vaccines and treatments found high levels of immunity made it nearly impossible, according to results from the COVID-19 “Human Challenge” trials in the U.K

The results, published May 1 in The Lancet Microbe, “raise questions about the usefulness of COVID-19 challenge trials for testing vaccines, drugs and other therapeutics,” Nature reported.

“If you can’t get people infected, then you can’t test those things,” Tom Peacock, Ph.D., a virologist at Imperial College London, told Nature.

Brian Hooker, Ph.D., chief scientific officer for Children’s Health Defense told The Defender, “The results show the power of natural immunity as compared to the many breakthrough infections in ‘naive’ vaccinated individuals.”

“Any assertion that vaccination-based immunity is more powerful than natural immunity is complete lunacy — the acquired immune system is a beautiful thing and vaccination is a cheaper and much less effective substitute,” he said.

Challenge trials require deliberately infecting healthy people with a virus, typically so scientists can understand infections and test the effectiveness of existing vaccines and treatments, and develop new ones.

When the U.K. government announced the first human COVID-19 trials in 2021, they were highly controversial.

Proponents argued the trials were necessary to speed the development of countermeasures and that the low relative risk was worth the benefit. Critics countered it was unethical to infect peoplewith a disease for which there is no cure.

After months of ethical debate, the first study launched in March 2021. In that study, researchers exposed 36 people ages 18-29 to the original strain of COVID-19 via nasal droplets.

About 53% of the participants eventually tested PCR-positive for COVID-19 but had very mild or no symptoms. And there was no correlation between symptom severity and viral load.

The second study, whose results were reported in The Lancet Microbe last week, infected people with COVID-19 who already had natural immunity because they were previously infected “by a range of variants,” Nature reported. Some were vaccinated and some weren’t.

Between May 6, 2021, and Nov. 24, 2022, scientists inoculated 36 people with different doses of SARS-CoV-2. They quarantined the subjects for 14 days and tested them for the virus during that time and throughout 12 months of follow-up.

When the first participants did not become infected, the researchers continued increasing the dose until it reached 10,000 times the original dose.

They were unable to induce sustained infection in any of the volunteers. Five of them later got mild infections during the Omicron period.

“We were quite surprised,” Susan Jackson, a study clinician at Oxford and co-author of the latest study, told Nature. “Moving forward, if you want a COVID challenge study, you’re going to have to find a dose that infects people.”

The study was funded by the Wellcome Trust and the U.K.’s Department of Health and Social Care.

Nature reported that another challenge trial is ongoing at Imperial College London, where participants are being given the Delta variant. However, that trial has also had problems infecting participants. The scientist leading that study, Christopher Chiu, told Nature that the level of infections study subjects are sustaining is “probably not enough for a study testing whether a vaccine works.”

They are continuing to try to develop ways to actually infect trial subjects so they can develop vaccines. Those methods include giving people multiple doses of the vaccine or finding people who have low levels of immune protection.

Chiu is heading up a consortium that has received a $57 million grant from the European Union and the Bill & Melinda Gates Foundation-backed CEPI, the Coalition for Epidemic Preparedness Innovations, to use challenge trials to develop inhaled and intranasal COVID-19 vaccines.

This grant was awarded in March and will focus on using human challenge trials to develop these vaccines. That is despite the challenges to infecting subjects reported in the human challenge trials so far.

In that study, more than a dozen teams will use human challenge studies to test experimental vaccines that are either inhaled or given through the nose to see if they can induce mucosal immunity in the nose, throat and lungs.

The researchers say they are developing new vaccines against betacoronoviruses, the subfamily of coronaviruses that includes COVID-19, and other seasonal viruses that cause common colds.

In 2022, CEPI launched a broader $200 million initiative to develop more vaccines for COVID-19 and other betacoronviruses.

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