A Covid-19 vaccine is urgently needed if we want to stop the spread of the virus and potentially prevent millions of additional deaths. We are now one step closer to that goal.
We have published the first results of our clinical trial of the ChAdOx1 nCoV-19 vaccine (also known as AZD1222), designed by the University of Oxford and developed in collaboration with AstraZeneca. Preliminary data shows that it is safe and induced a strong antibody response in all vaccinated volunteers, suggesting that an effective vaccine may be within reach.
This test was the first time that the vaccine was administered to humans: 543 healthy adults aged 18 to 55 years were vaccinated with a single dose of ChAdOx1 nCoV-19. A further 534 people were given a control vaccine that produces similar minor reactions, including redness at the injection site and mild pain. Volunteers have their immune response (both antibody and T-cell levels) monitored for at least 12 months, and will also be observed to see if they develop Covid-19 or not.
Preliminary data from the trial clearly demonstrates that the vaccine induces an antibody response within 28 days. This response is in a range similar to that of people who have recovered from Covid-19, encouraging that the vaccine can protect most people against infection.
Ten volunteers also received a second booster dose of the vaccine. This increased the antibody response to even higher levels, and 100% of the blood samples in this group showed neutralizing activity against Covid-19 infection in a laboratory setting.
The vaccine also induced T cells that specifically recognize SARS-CoV-2, the virus that causes Covid-19. It is encouraging to see both antibody and T-cell responses, as together they are the correct type of immune response that could lead to protection against the virus. Importantly, the vaccine demonstrates an acceptable safety profile, without vaccine-induced serious adverse events, that is, without significant side effects.
We are confident in testing the vaccine in humans after encouraging testing with rhesus macaque monkeys and mice. These had shown that the vaccine was safe and induced a robust immune response. Significantly, the vaccinated monkeys protected themselves from serious illness after they were challenged with a much higher dose of SARS-CoV-2 than humans would find through natural exposure.
How does the Covid-19 vaccine work?
Vaccines work by training the immune system to recognize and fight infectious agents (pathogens), such as bacteria and viruses. Vaccines do this by presenting the immune system with an easily identifiable part of a pathogen, which the immune system remembers so it can respond quickly if it encounters that same pathogen in the future.
Most vaccines in development for SARS-CoV-2, including this one, focus on presenting the spike protein that decorates the virus’s surface. It is this protein that allows the virus to enter human cells by binding to a molecule on its surface called ACE2.
There is a wide range of approaches to vaccine design; ChAdOx1 nCoV-19 is what is known as a viral vector vaccine. To make this vaccine, particles from a different and harmless virus (called ChAdOx1) are loaded with the DNA portion of the SARS-CoV-2 that instructs cells on how to build the spike protein.
When these ChAdOx1 particles infect human cells, the coronavirus DNA is “expressed” and forms the spike protein for the immune system to respond to. Important for vaccine safety, the viral vector cannot replicate and cause continuous infection.
The ChAdOx1 viral vector has been used to make eight vaccines in clinical trials for other human diseases, including Mers (Middle East respiratory syndrome), a coronavirus related to SARS-CoV-2.
What happens next? Crucially, we must demonstrate that the vaccine is effective, resulting in significantly lower (ideally zero) cases of Covid-19 in the group vaccinated with ChAdOx1 nCoV-19 versus the control group. Falling infection rates in the UK is an excellent result for the nation’s health, but it may compromise the ability to show this.
If there are no cases of Covid-19 in the group receiving the control vaccine, comparing that group with the vaccinated group would be meaningless. It may be possible to deliberately infect people with the virus in the future (after careful consideration of the ethical implications), but it is not currently allowed.
For this reason, a second trial was launched in approximately 10,000 individuals in the UK, targeting healthcare workers, and further trials are underway in Brazil and South Africa, where infection rates are much higher. The expanded UK trial will include children and older adults to estimate the vaccine’s effectiveness in these age groups. Immune responses in people over the age of 70 are often lower than in younger adults.
It is essential to monitor the vaccine-induced immune response for a period of at least one year, to estimate whether booster injections will be needed and, if so, how often. My personal prediction, based on decreased antibody levels in people infected with other types of coronaviruses, rather than data from the current vaccine trial, is that we will likely need annual boosters, similar to annual flu punctures.
Finally, if the vaccine is to be effective, it would require rapid manufacturing of billions of doses to supply the world. To facilitate this, AstraZeneca has already started a large-scale vaccine manufacturing program, with the goal of having hundreds of millions of doses delivered by the end of 2020. There are agreements to provide the vaccine to low- and middle-income countries . and also to the United Kingdom, Europe and the United States.
This article was originally published in The Conversation by Rebecca Ashfield at Oxford University. Read the original article here.
