LONDON – The COVID-19 vaccine developed by Astrazeneca plc and Oxford University has been approved by the U.K regulator, with the first doses being shipped on Dec. 30 and a mass vaccination program due to begin on Jan. 4.

AZD-1222, now named COVID-19 Vaccine Astrazeneca, is authorized for emergency use and will require two doses for durable effect.

However, the U.K. Medicines and Healthcare products Agency (MHRA) said that rather than four weeks, these can be between four and 12 weeks apart. That is based on data showing there is protection against severe SARS-CoV-2 infection from around 22 days after the first dose.

Because of logistical constraints, the interval between dose one and dose two in the phase III trial on which the approval is based ranged from four to 26 weeks. An analysis carried out by the MHRA and referenced in the label on the vaccine showed increased immunogenicity was associated with a longer dose interval. Overall, MHRA concluded vaccine efficacy at 22 days post dose one was 73%.

The U.K. Joint Committee on Vaccination and Immunization (JCVI), which advises on how vaccines administration is prioritized, said the aim now should be to give as many people as possible in at risk groups their first dose, rather than administering two doses in as short a time as possible.

The U.K. has an advanced purchase agreement for 100 million doses of the vaccine, which Astrazeneca has committed to supply at cost – of $4 per dose – for the duration of the pandemic.

The EU has ordered 400 million doses and the U.S. 300 million. Astrazeneca said it is building up manufacturing capacity to deliver 3 billion doses of the vaccine globally in 2021, pending regulatory approvals.

Unlike the approved Pfizer Inc./Biontech and Moderna Inc. mRNA COVID-19 vaccines, which must be kept at ultra-low temperatures, AZD-1222 can be stored, transported and handled at normal refrigerated conditions of between 2 and 8 degrees Celsius for at least six months, meaning it can be administered through existing vaccines cold chains.

To date, more than 600,000 people in the U.K. have been vaccinated with the Pfizer/Biontech vaccine, which MHRA became the first regulator to approve on Dec.2.

The number of doses available and the handling requirements of AZD-1222, coupled with efficacy after two weeks, will change the pace of the immunization program in the U.K.

“The regulator’s assessment that this is a safe and effective vaccine is a landmark moment,” said Andrew Pollard, head of the Oxford Vaccine group and chief clinical investigator. “Though this is just the beginning, we will start to get ahead of the pandemic.”

The approval of AZD-1222 came as the U.K. faces unprecedented levels of SARS-CoV-2 infections, with 53,000 cases diagnosed on Dec. 29 and more patients in hospital than in April, at the height of the first wave of the pandemic.

Pascal Soriot, CEO of Astrazeneca said, “millions of people in the U.K” will get access to the vaccine. “It has been shown to be effective, well-tolerated, simple to administer, and is supplied by Astrazeneca at no profit.”

“At a time when we see the pandemic accelerating beyond our control, a rapid, efficient vaccination program with good population coverage is our only way out,” said Daniel Altmann, professor of immunology at Imperial College London, commenting on the approval. “This vaccine induces good levels of neutralizing antibodies and T cells.”

With two vaccines now being rolled out and very substantially more doses, “it starts to look realistic” that there could be good coverage by the spring or early summer, Altmann said.

It works against new strains

The surging rate of infection in the U.K. is being driven by the recently detected B.1.1.7 variant of SARS-CoV-2, which computer modeling suggests is 70% more transmissible than other variants circulating in the country.

The variant has an array of mutations, including some in the spike protein that the virus uses to enter host cells, and against which many COVID-19 vaccines, including Astrazeneca’s and Pfizer/Biontech’s, are designed to generate an immune response. That has led to concerns efficacy of the vaccines would be compromised.

In a statement, the Oxford Vaccines group said there is no evidence so far that its vaccine will be any less effective against this new strain of the virus. ”Changes in the virus are being monitored closely, and it’s important we continue to remain vigilant for changes in the future,” the statement said.

The JCVI’s recommendation on Dec. 30 that the first dose of AZD-1222 should be administered to as many people as possible, rather than focusing on administering two doses as soon as possible, also applies to the Pfizer/Biontech vaccine.

In the context of the epidemiology of COVID-19 in the U.K. in late 2020, priority should be given to promoting rapid, high levels of vaccine uptake amongst vulnerable persons, JCVI said. “Given data indicating high efficacy from the first dose of both Pfizer/Biontech and Astrazeneca vaccines, the committee advises that delivery of the first dose to as many eligible individuals as possible should be initially prioritized over delivery of a second vaccine dose. This should maximize the short-term impact of the program.”

The JCVI decision to allow both the currently U.K. authorized vaccines to be given with a greater delay between doses, to maximize the numbers getting one dose as rapidly as possible is “a sensible one,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “It cannot have been an easy decision, since the evidence on the efficacy of one dose [of AZD-1222] was more limited, but the crisis in the U.K. requires more than the usual regulatory approach.”

In the face of rising infection rates across Europe, EMA responded to the MHRA approval with an update on its rolling review of AZD-1222. The latest clinical package was received on Dec. 21 and is currently being assessed, but the agency said it has asked for more data.

“Additional scientific information on issues related to quality, safety and efficacy of the vaccine is deemed necessary to support the rigor required for a conditional marketing authorization and this has been requested from the company,” EMA said in a statement on Dec. 30.

More trial data coming in Q1 2021

The agency also noted more information from ongoing clinical trials is expected early next year and interim data from a large the U.S. phase III are expected in Q1 2021, implying EMA might wait for more data to be available.

Oxford University received early backing from the Coalition for Epidemic Preparedness Innovations (CEPI), when its vaccine project first got off the ground in January. Welcoming the MHRA approval 11 months later, Richard Hatchett, CEO of CEPI said it should pave the way for similar decisions by other regulators and for World Health Organization prequalification in the days and weeks ahead.

“The Oxford/AstraZeneca COVID-19 vaccine is extremely attractive in that it is inexpensive, scalable, and can be stored at 2-8 degrees Celsius,” Hatchett said. “These attributes will enable its use worldwide, including in low-income and middle-income countries, and the large supplies that will become available in 2021 mean that this vaccine could be a game changer in terms of our efforts to end the acute phase of the pandemic.”