100-day vaccine project in doubt without new human trial regulations

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Experts have warned that plans to develop vaccines in just 100 days to halt future pandemics could be undermined without a major overhaul of clinical trials. 

Institutions including Wellcome and the Coalition for Epidemic Preparedness Innovations (Cepi) have recently launched ambitious plans to create prototype vaccines for the 25 viral families known to infect humans. 

The idea is to have vaccines ready to deploy within 100 days of a new virus being detected – rather than the 11 months it took to create the first Covid jab. 

Non-pharmaceutical interventions would be used to suppress the spread of a new pathogen for the short time it would take for the vaccine to arrive.

But experts say the strategy could fall victim to a “catch 22” unless a new way can be found to test the efficacy of vaccines in humans. This is because phase three trials currently necessitate large numbers of people catching the virus.

“There are lots of suggestions that future pandemic strategy should be ‘keep transmission low and develop an efficacious vaccine within a few months,’” noted Prof Adam Kucharski, an infectious disease epidemiologist at the London School of Hygiene and Tropical Medicine, on Twitter this week.

But “to ensure little transmission and a successful vaccine efficacy trial, would need to consider alternative routes to licensure,” he added, referencing human challenge studies or surrogates of protection.

A modelling study published in the journal, Vaccine, demonstrates the dilemma: to run a randomised ring vaccination trial for Nipah, a virus with a fatality rate of up to 70 per cent, would take 516 years under current – very low – epidemic conditions. 

Vaccine development timeline

The phase three efficacy trials for the Covid vaccines involved tens of thousands of participants who were split into two groups – half were given the coronavirus shot, half received a placebo. 

Only when enough people had contracted Covid could the researchers establish how effective the vaccines were by comparing the outcomes across the two groups.

In Pfizer’s phase three study, this point was reached when 170 of the 43,000 volunteers involved caught coronavirus. Even then, the Covid vaccine trials were held in coronavirus hotspots, such as the United States, South Africa and Brazil so that enough people got infected quickly.

Dr Natalie Dean, an assistant professor of biostatistics at Emory University in the US and co-lead author of the report, told The Telegraph that high case numbers for Covid were a “silver lining”; without them, the vaccines could not have been quickly tested and deployed.

“Not only was [widespread Covid transmission] a silver lining, but it did accelerate dramatically the accrual of data… trials were just so insanely fast,” she said. 

According to Cepi, leading vaccine regulators, including representatives from the MHRA, are already looking at ways to “reform the vaccine ecosystem” in a bid to solve the problem. But there is no single solution that would cover all pathogens. 

Human challenge trials – where volunteers are deliberately infected – could work to test the efficacy of vaccines for  relatively mild diseases. But the same strategy would not work for viruses such as Nipah, where the death rate is high and there is currently no cure. 

Dr Dean said solutions would look different depending on a diseases’ profile. For Ebola – another disease with a high fatality rate – vaccine efficiency was established by deploying a jab under an emergency licence in tight rings around known cases. 

Most likely future pandemics

Because the risk of death from Ebola was so high for those involved, the limited use of an experimental vaccine could be justified from an ethical standpoint.

Dr Dean said that where emergency human trials could not be justified, animal models could be used to garner early data on efficacy. 

Scientists might also use so-called “surrogates of protection” – biomarkers such as T-cells or antibodies which are strong predictors of a solid immune response – to test vaccines in test tubes in a lab. This is how some proponents of the 100-day target see the strategy working. 

Nevertheless, Dr Melanie Saville, director of vaccine research and development at Cepi, said there needs to be a “paradigm shift” in pharmaceutical regulation for this to work.

Cepi is seeking to help create prototype vaccines against all viral families known to infect humans, and to conduct phase one and two safety and efficacy trials before any outbreak occurs. 

The aim is also to have a global network of clinical trial sites ready to go in case of a crisis, Dr Saville said, stressing that the 100-day target would not “be at the cost of safety”.

“You can only demonstrate efficacy decisively when you have a prevalent disease,” added Dr Richard Hatchett, Cepi’s chief executive. “The 100-day goal aspires to rapidly deliver a definitive countermeasure as a tool (hopefully) to suppress further transmission – in concert with other public health interventions – and if at all possible prevent a pandemic from unfolding.  

“We have not assumed that we would have full efficacy data at 100 days, and if the disease has been suppressed, then what you have is a candidate vaccine in the bank in case the disease re-emerges.  

“Obviously, if the disease has already become pandemic at 100 days the opportunities for directly demonstrating efficacy will be greater. How the vaccine would be used, in the latter case, would be based on a risk-benefit assessment,” he said.

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