LONDON – A second phase III trial of Johnson & Johnson’s adenoviral-vectored COVID-19 vaccine is starting in the U.K. this week, amid concerns the positive news from the Pfizer Inc./Biontech SE vaccine study will deter volunteers from coming forward to take part.
The U.K. arm of the phase III study of JNJ-78436735 is due to recruit 6,000 participants at 17 centers around the country.
“I’m intrigued and concerned to see what effect Pfizer’s announcement will have on willingness to participate,” said Adam Finn, professor of paediatrics, who is leading the study at Bristol University Hospital. “If there is to be a solution to the pandemic, we need a range of vaccines, in sufficiently large volumes. The effort needs to continue; studies do need to go forward,” Finn said.
The trial investigators particularly want to attract volunteers who are most vulnerable to the effects of COVID-19, including front-line health and care workers, and people from Black, Asian and ethnic minority backgrounds.
In July, as the first phase III U.K. COVID-19 vaccine trial of Astrazeneca plc and Oxford University’s AZD-1222 got off the ground, the National Health Service opened a registry for volunteers to put themselves forward to take part. There currently are 317,399 names on the register and people living near the 17 centers will be getting emails this week inviting them to join the J&J trial.
To date, around 25,000 people have been recruited to COVID-19 vaccines trials in the U.K., including 13,000 who are taking part in the Astrazeneca/Oxford University phase III, and 10,000 in the phase III study of Novavax Inc.’s NVX-CoV2373.
“Because we have got a national registry, that has accelerated the ability to run trials,” said Kate Bingham, head of the U.K. government Vaccines Taskforce, set up to ensure access to a range of different vaccines and to put the U.K. at the forefront of COVID-19 vaccines research. Novavax decided to launch the phase III trial of its attenuated, adjuvanted vaccine in the U.K. after being approached by the taskforce.
The U.K. arm of the second J&J phase III, co-funded by the Vaccines Taskforce, is due to complete recruitment in March 2021.
The taskforce has sealed advance purchase agreements for 350 million doses of six different vaccines based on four different delivery mechanisms. The order for 30 million doses of the J&J vaccine will be available from mid-2021, if the product is approved.
Three of the pre-ordered vaccines are being manufactured in the U.K. The U.K. also has committed £500 million (US$659.2 million) to the international COVAX fund that will procure COVID-19 vaccines and therapies for low- and middle-income countries.
The J&J vaccine entered a single dose U.S. phase III in September, which will recruit up to 60,000 volunteers. In the second trial opening in the U.K., two doses of the vaccine will be administered 57 days apart. The phase I/II study showed a single dose induced a robust immune response, but J&J said multiple doses and dosing regimens are being evaluated, in order to assess long-term efficacy.
The ‘need to carry on’
The news that Pfizer/Biontech’s BNT-162b2 showed 90% efficacy in an interim analysis conducted after 94 confirmed cases of COVID-19 in participants is encouraging. However, there are no guarantees the final result will be as good, or that BNT-162b2 will be suitable for all.
In addition, there is limited manufacturing capacity and difficult logistics for the product, which must be stored at minus 70 degrees centigrade.
“We aren’t going to have enough doses, or the logistical power to vaccinate everyone very quickly, said Saul Faust, director of the National Institute of Health Research facility at Southampton University, who is principal investigator for the U.K. arm of the J&J phase III study.
“It’s estimated the under-50s would get it [the Pfizer vaccine] by the second half of 2021, so [it will be] some time before the bulk of the population get the vaccine; there are technical difficulties of manufacturing and deployment,” Faust said. “Pfizer/Biontech is not the end of the story; it’s the beginning of the story. People have asked questions as they come forward for appointments, but have understood the need to carry on.”
The Pfizer announcement is “exciting” because “now we know spike protein vaccines work,” said Faust. “But we just don’t know how each of the vaccines behaves and which will generate the best short- and long-term immunity.”
Bingham agreed, saying, “We must not take our focus off continuing the important research to work out which vaccines work best for different people, to provide long-lasting, effective protection against COVID-19.”
To help in that evaluation, the Vaccines Taskforce has commissioned the development of assays to make it possible to compare the effects of different COVID-19 vaccines.
A national immunization agency is now drawing up protocols for trials to test combinations of any approved COVID-19 vaccines in 2021. That could, for example, involve giving an initial dose of an mRNA vaccine, followed by a booster from one that is adenoviral vectored.
“A combination of vaccines could provide broader immunity. We have four different types of vaccine, so we can maximize the possibility of getting the best combination,” Bingham said.
There is plenty of precedent for testing vaccine combinations, and there is no need for further preclinical research, said Finn. “Safety in people is better than you can generate in animals,” he said.