An Overview of the AstraZeneca-Oxford COVID-19 Vaccine

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While some vaccine makers are using new approaches to fight the coronavirus disease 2019 (COVID-19), others are turning to more established methods to end the pandemic.

AstraZeneca and Oxford University have been working on an adenovirus-based vaccine, ChAdOx1 nCoV-19 (AZD1222). The vaccine is a viral vector vaccine that uses a modified adenovirus—the virus that causes the common cold—that contains genetic material from the SARS-CoV-2 virus. The vaccine was developed quickly since this vaccine technology has been around for decades.

Oxford had been studying adenovirus-based vaccines for a number of other diseases like the Zika virus when COVID-19 emerged. Researchers adapted a weakened chimpanzee adenovirus to develop the vaccine, and a Phase 1 trial began in April 2020, with more than 1,000 vaccinations given in the United Kingdom.1

Initial Phase 3 trial results were published in early December and investigated how well the vaccine worked in more than 11,000 of the nearly 24,000 people over the age of 18 enrolled across four trial groups in the United Kingdom, Brazil, and South Africa.2

There has been some controversy surrounding this vaccine, with dosing discrepancies in some study groups, and a move by the U.S. Food and Drug Administration (FDA) to pause the U.S. trial because of unexplained illness. The FDA restarted the trial after reviewing the safety data.3

In addition, about a dozen European countries that had authorized the vaccine temporarily paused vaccinations due to concerns about a potential link to blood clots. After a review, the European Medicines Agency (EMA) announced on March 18 that it did not find an association with an overall increased risk of blood clots but did find a possible association with very rare cases of blood clots. The EMA concluded that the benefits of the vaccine still outweigh the risks of side effects, especially considering that COVID-19 itself can lead to blood clots.4 The World Health Organization (WHO) also released a statement urging countries to proceed with vaccination.5

There are not any hearings scheduled yet on an emergency use authorization by the FDA, and the U.S. clinical trial is scheduled to last until September 2021.6
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How It Works

The AstraZeneca-Oxford vaccine is a recombinant adenoviral vector vaccine. Recombinant vaccines use a small piece of genetic material from a pathogen, like SARS-CoV-2, to trigger an immune response. A specific piece of the virus can be targeted, and recombinant vaccines are generally safe to use in a large population of people—even those with chronic health problems or people who are immunocompromised.

The AstraZeneca-Oxford vaccine is a recombinant adenovirus vaccine that uses a weakened live pathogen. One drawback of recombinant adenoviral vector vaccines is that booster shots may be required over time. Examples of similar types of recombinant vaccines (that do not use live pathogens) are pneumococcal vaccines and vaccines for meningococcal disease.7 While recombinant vaccines are common, the only commercially available adenovirus-based vaccine of this type is a rabies vaccine for animals.

Adenovirus vaccines can pose some problems in that the adenovirus is so common that the vaccine may not be as effective once booster doses are given, or that some people may already have immunity to the virus used in the vaccine.

The AstraZeneca-Oxford vaccine was tested using two doses given about a month apart. The dosing used in the trials is unclear—with different accounts of the dosing changes first uncovered by Reuters news service. Reporters with the news agency were given two different answers by AstraZeneca and Oxford about whether a subgroup in the U.K. arm of the study received half doses of the vaccine purposefully or by accident. The discrepancy was uncovered after preliminary results were published.8

How Effective Is It?

Whether by accident or on purpose, the dosing change appears to have been lucky. According to the trial report, the AstraZeneca-Oxford vaccine is about 70% effective on average. However, this average was calculated after a 62% effective rate was observed in people who received the full vaccine dose compared with 90% effective in those who received the half dose.2 Additional reviews are ongoing, and it remains unclear at this time why a half-dose of vaccine might have worked better than a full second dose.

When Will It Be Available?

It is widely authorized across Europe for use in adults 18 and older despite the initial arguments over whether the half dosing of the vaccine was intentional and temporary pauses in both the trials and vaccinations. The company announced in November that trials are still underway around the world, but that—pending regulatory approvals—as many as 3 billion doses could be available in 2021.9

The vaccine may be able to be more easily distributed than some other options. Rather than extremely cold temperatures like some other vaccine options, the AstraZeneca-Oxford vaccine requires only standard refrigeration, and is estimated to cost around $3 to $4 per dose.10

If and when the vaccine might be available in the United States is a big question. The Centers for Disease Control and Prevention (CDC) is leading vaccination efforts, and all orders of the COVID-19 vaccine, regardless of the manufacturer, will go through the agency. CDC is overseeing the distribution of vaccines, too. CDC’s Advisory Committee on Immunization Practices (ACIP) has made recommendations on how to prioritize vaccine supplies. Healthcare workers and people living in long-term care facilities were the first priority groups to receive authorized COVID-19 vaccines.

The CDC estimated that it will take several months before the supply of vaccines catches up to the demand. Guidance on who will receive the vaccine and when will be decided as supplies become available. The U.S. alone has a population of about 330 million.11

State and local health departments are coordinating efforts to distribute doses of the vaccines as they become available. The vaccine should be available both in physician offices and retail locations like pharmacies that administer other vaccines.

Who Can Get the AstraZeneca Vaccine?

The initial clinical trial for the AstraZeneca-Oxford vaccine focused on people aged 18 to 55, and new trials with people older than 55 began in August. There had initially been trials involving children, but that group was removed from trial data in mid-December. AstraZeneca and Oxford have not made any statements on the change. In February, the University of Oxford announced the launch of a new children’s trial that will enroll 300 participants ages 6 to 17.12

Side Effects and Adverse Events

Generally, side effects of COVID-19 vaccines have included arm pain, swelling, and redness where the vaccine was injected. There have been a few other adverse effects reported, though, including one that resulted in a pause in the AstraZeneca-Oxford clinical trial.2

Adverse reactions are considered to be medication reactions directly caused by a vaccine, whereas a side effect is a physical reaction to a medication. The preliminary report on the vaccine published in The Lancet revealed generally good results in terms of side effects, but there were a few concerning adverse reactions.

There were three cases of transverse myelitis—a condition where there is inflammation of the spinal cord—in people who received the vaccine. These illnesses were determined to be unlikely to have been caused by the vaccine, according to the trial report. A number of deaths were also reported in the study (most in the control group), but those deaths were unrelated to the vaccine and were due to incidents like traffic accident and homicide.2

Funding and Development

The vaccine was developed through a partnership between Oxford and AstraZeneca. Funding support for the study was also provided by United Kingdom Research and Innovation, the Bill & Melinda Gates Foundation, the NIHR Oxford Biomedical Research Centre, and the Thames Valley and South Midland’s NIHR Clinical Research Network.

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