LONDON – Astrazeneca plc is to get up to $1.2 billion from the new U.S. COVID-19 vaccines program, Operation Warp Speed, to support further development and manufacturing of a vaccine developed at Oxford University’s Jenner Institute.

The company said it will begin to ship the product in September 2020, with the U.K. and U.S. first in line for deliveries.

The development program, agreed with the Biomedical Advanced Research and Development Authority (BARDA), includes a U.S. phase III trial with 30,000 participants. In parallel with clinical development, Astrazeneca will work with BARDA’s Centers for Innovation and Advanced Development in Manufacturing, on technology transfer and scaled-up manufacturing of the vaccine in the U.S.

Astrazeneca said to date it has booked orders to supply at least 400 million doses of the recombinant adenovirus vaccine, of which 300 million doses will go to the U.S., with deliveries beginning in October.

“This contract with Astrazeneca is a major milestone in Operation Warp Speed’s work toward a safe, effective, widely available vaccine by 2021,” said Alex Azar, secretary of the Department of Health and Human Services. This is the fourth COVID-19 vaccine candidate to receive BARDA support for late-stage development and manufacturing.

To date, Astrazeneca has secured manufacturing capacity for 1 billion doses. The Cambridge, U.K.-based company is in discussions with the world’s largest vaccine manufacturer, the Serum Institute of India, and other potential partners, to further increase production and distribution.

Betting on progress

The vaccine “may not work,” but Astrazeneca said it is committed to progressing the clinical program with speed and scaling up manufacturing at risk. “We will do everything in our power to make this vaccine quickly and widely available,” said Pascal Soriot CEO, promising to ensure access around the world, in an equitable manner.

Talks are in progress with the World Health Organization, the Gavi vaccines alliance and the Coalition for Epidemic Preparedness and Innovation (CEPI), for the fair allocation and distribution of the vaccine, formerly called ChAdOx1 nCoV-19 and now known as AZD-1222. Astrazeneca said it also is in discussion with governments to arrange access.

The change of name reflects the fact that Astrazeneca has now finalized the license agreement with Oxford University for the vaccine, which currently is in a phase I/II trial assessing safety, immunogenicity and efficacy in more than 1,000 healthy volunteers, ages 18 to 55.

Data from the study are expected shortly. Astrazeneca said if that trial is positive, it will run late-stage trials in a number of countries.

The potential $1.2 billion support from BARDA is a huge shot in the arm for the project and dwarfs the support received from the U.K. government. Most recently, on May 18, it announced £64.5 million (US$78.9 million) for the Oxford vaccines group to help accelerate its work. That followed an April 21 announcement of £20 million.

The U.K. government also has put £250 million into CEPI, some of which has flowed back to the Oxford vaccine, which is one of seven projects CEPI is backing to fast track development of vaccines against COVID-19.

The announcement of the BARDA deal is not anticipated to have any significant impact on Astrazeneca’s financial guidance for 2020, with expenses to progress the vaccine largely offset by public funding. “We would like to thank the U.S. and U.K. governments for their substantial support to accelerate development and production of the vaccine,” Soriot said.

Questions remain

AZD-1222 uses a replication-deficient chimpanzee viral vector, ChAdOx1, to deliver the genetic code for the spike protein via which SARS-CoV-2 invades host cells, priming the immune system to react against the virus.

Vaccine candidates against Lassa fever, Nipah virus infection, MERS and SARS-CoV-1 using the ChAdOx1 vector have been administered to more than 330 people in 12 clinical trials. A further 6,000 individuals have been vaccinated with a similar vector. Based on that experience, it is known ChAdOx1 can generate a strong immune response from a single dose.

On May 13, Sarah Gilbert, a professor of vaccinology at Oxford University, and colleagues working on the project, published a preprint on the Biorxiv server reporting that a single vaccination with half the dose of AZD-1222 being administered in the human trial induced humoral and cellular responses in rhesus macaques.

Virus-specific neutralizing antibodies were detectable in all vaccinated animals before challenge, while there were none in controls. No pneumonia was observed in vaccinated animals when challenged with SARS-CoV-2, and importantly, there was no evidence of immune enhanced disease, as had been observed in preclinical studies of vaccines against SARS-CoV-1.

However, vaccinated animals did have virus in their respiratory tracts, albeit at a lower level than controls. Viral RNA also was detected in nose swabs from all animals, with no difference in viral load between the vaccinated and the control group.

Babak Javid, professor at Tsinghua University School of Medicine in Beijing, China and consultant in infectious disease at Cambridge University Hospitals in the U.K., said it is not without precedent for a vaccine to protect an individual against disease but not prevent them from passing on the infection.

“The current whooping cough vaccine also works by preventing disease rather than infection,” said Javid. The risk that immunized individuals can still transmit infection is “an important consideration” if there is not universal vaccine coverage, he said.

Jonathan Ball, professor of molecular virology at Nottingham University, agreed it is concerning the same amount of viral RNA was detected in the noses of vaccinated and control animals in the AZD-1222 challenge trial.

“If this represents infectious virus and a similar thing occurs in humans, then vaccinated people can still be infected [and] shed large amounts of virus, which could potentially spread to others,” Ball said.

Gilbert et al note the macaques were challenged with a high dose of SARS-CoV-2, via multiple routes. That does not reflect realistic human exposure. “Whether a lower challenge dose would result in more efficient protection of the upper respiratory tract remains to be determined,” they said.