Global quest underway to accelerate COVID-19 vaccine trials

CHICAGO, July 20 (Reuters) – Scientists are working on a benchmark for the effectiveness of the COVID-19 vaccine that would allow drugmakers to conduct smaller, faster human trials to bring them to market and cope with a huge global vaccine shortage.

Researchers are trying to determine what level of COVID-19 antibodies a vaccine must produce to provide protection against the disease. Regulators are already using such benchmarks – known as correlates of protection – to assess influenza vaccines without requiring large, lengthy clinical trials.

“You could use it to predict the effectiveness of a vaccine, which will be more important because we are less able to conduct placebo-controlled trials,” said Stanley Plotkin, inventor of the rubella vaccine and expert in rubella. correlates of protection.

“Information is pouring in,” he said. “By the end of this year, I think there will be enough data to convince everyone.” A benchmark set for COVID-19 would allow drugmakers to conduct vaccine trials on a few thousand people, about a tenth the size of studies conducted to gain clearance for currently widely used coronavirus vaccines, said to Reuters researchers and drug makers.

These studies, involving tens of thousands of volunteers, compared the rate of COVID-19 infections in people who received the vaccine with the rate in participants who received a placebo.

Such randomized controlled trials may no longer be considered ethical in some countries because researchers cannot make a dummy vaccine for people for whom an effective vaccine is widely available. Additionally, many of the new clichés are being developed by small companies that might not be able to conduct very large trials without government funding or a partner with generous pockets.

With a correlate established, drugmakers could test blood samples from a smaller number of trial participants who receive an investigational vaccine to see if they are producing that baseline level of protective antibodies.

Such a reference is “urgently needed” to help overcome the challenges facing vaccine developers and increase vaccine availability, Dr Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai, wrote this month at New York in the journal Nature.

At the end of last month, researchers at the University of Oxford proposed a potential correlate of protection based on the antibodies found in people who had received the AstraZeneca (AZN.L) vaccine. The work is waiting to be evaluated by other scientists.

The results of a US-backed study of Moderna’s vaccine (MRNA.O) are expected to be published in a medical journal later this summer. “We are writing the paper right now,” said Dr Peter Gilbert, biostatistician at the Fred Hutchinson Cancer Research Center.

Some vaccine experts question whether antibody levels will be a strong enough indicator of protection. It is believed that other components of the immune system, such as T cells and B cells, provide important defenses against COVID-19, but are more difficult to measure.

This is claimed by some of the top vaccine experts at Pfizer (PFE.N), maker with BioNTech of one of the most effective COVID-19 vaccines, produced in largest quantities in the world.

It’s also possible that each different type of coronavirus vaccine will require its own correlate, some experts have said. Drugmakers working on a new type of vaccine likely couldn’t rely on the correlates based on Moderna’s messenger RNA firing, they say.

BRIDGING THE GAP

Meanwhile, vaccine developers are trying to design acceptable substitutes for huge, placebo-controlled trials. Some aim to show that their injection elicits antibody responses at least as good as those observed with currently authorized injections.

European and UK health regulators are working with companies to set standards for these so-called “immunobridging” studies. The U.S. Food and Drug Administration declined to say whether it would accept such trials for next-generation vaccines.

“It doesn’t have to be an established correlate of protection, but we have to (…) arrive at the right predefined criteria, because we cannot risk a second generation vaccine (…) being d ‘low or modest vaccine efficacy. FDA vaccine chief Dr Marion Gruber told other regulators at a World Health Organization meeting in May. “It would undermine confidence in the vaccine business.”

The Italian ReiThera Srl is developing a vaccine using technology similar to that of AstraZeneca and will try to demonstrate that its vaccine is at least as effective.

The company has an agreement in principle on the design of the trials with European and UK regulators, Stefano Colloca, senior director of ReiThera, told Reuters. Massive clinical trials are “no longer ethical and feasible in most countries of the world,” he said.

French biotech Valneva (VLS.PA) and Taiwanese company Medigen Vaccine Biologics Corp (6547.TWO) plan to test their vaccines against the AstraZeneca vaccine, although the two use different technology. The design of the Valneva trial has been approved by UK regulators. Medigen has the green light from Taiwan.

Sanofi (SASY.PA), along with its partner GlaxoSmithKline (GSK.L), and Medicago in Canada continue to opt for placebo-controlled trials involving thousands of participants, including in countries with high infection rates and where fewer licensed vaccines are available.

NEED TO BOOSTER?

The hunt for a correlate is ongoing from the UK to the US and Australia. Scientists are comparing antibody levels in vaccinated people who have been infected with COVID-19 to those who have not, to find a threshold of protection that makes the difference.

Researchers at the University of Oxford said work is needed to determine the correlates of emerging viral variants, such as the highly transmissible Delta which has quickly become globally dominant. read more Their proposed antibody model is based on test volunteers who had primarily contracted the previous Alpha variant, first identified in the UK.

US government-backed scientists are studying infections in people who have received the Moderna vaccine. Moderna spokesman Ray Jordan said the company is also working on the analysis and will release updates when they are available.

The correlated baseline could also indicate when and if people need boosters.

Pfizer has requested permission for a third booster dose of its vaccine, citing evidence of declining levels of neutralizing antibodies. But the company rejected the idea that these same antibodies could be used to predict the effectiveness of the vaccine.

“No official timetable is in place to establish correlates of protection,” said a spokesperson for Pfizer. “We will continue to work with the scientific community to better understand what immune responses, whether neutralizing or not, could help protect.”

Reporting by Julie Steenhuysen in Chicago and Ludwig Burger in Frankfurt; Additional reporting by Emilio Parodi in Milan, Matthias Blamont in Paris, Michael Erman in Maplewood, New Jersey, Allison Martell in Toronto and Ben Blanchard in Taipei; Editing by Michele Gershberg and Bill Berkrot

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