the Oxford coronavirus vaccine works and what's next
On Monday, we published the first results of our clinical trial of the Chadox1 nCov-19 vaccine, also known as AZD1222, developed by the University of Oxford and developed in partnership with AstraZeneca. Preliminary data shows that it is safe and causes a strong antibody reaction in all vaccinated volunteers, suggesting that an effective vaccine may be within reach.
This trial was the first time the vaccine was given to humans: 543 healthy adults aged 18-55 were vaccinated with a single dose of Chadox1 nCov-19. Another 534 people received the control vaccine, which gives similar minor reactions, including redness of the injection site and slight pain. The volunteers monitor their immune response — both antibodies and T — cell levels-for at least 12 months, and will also monitor whether they develop Covid-19.
Preliminary research data clearly show that the vaccine induces an antibody response within 28 days. This response is in the same range as in people who have recovered from Covid-19, which gives hope that the vaccine can protect most people from infection.
Ten volunteers also received a second" booster " dose of the vaccine. This increased the antibody response to even higher levels, and 100% of blood samples from this group showed neutralizing activity against Covid-19 infection in the laboratory.
The vaccine also induced T cells that specifically recognize Sars-Cov-2, the virus that causes Covid-19. It is encouraging to see both antibodies and T-cell responses, since together this is the right kind of immune response that can lead to protection from the virus. It is important to note that the vaccine demonstrates an acceptable safety profile, without any serious side effects caused by the vaccine, that is, without serious side effects.
We confidently tested the vaccine in humans after encouraging trials with mice and rhesus macaques. They have shown that the vaccine is safe and causes a sustained immune response. It is important to note that vaccinated monkeys were protected from severe disease after being challenged with a much higher dose of Sars-Cov-2 than humans might have faced with natural exposure.
How does this vaccine work?
Vaccines work by training the immune system to recognize and fight infectious agents or pathogens, such as bacteria and viruses. Vaccines do this by presenting the immune system with an easily identifiable part of the pathogen that the immune system remembers so that it can respond quickly if it encounters the same pathogen in the future.
Most vaccines being developed for Sars-Cov-2, including this one, focus on representing the spike protein that adorns the surface of the virus. It is this protein that allows the virus to enter human cells by binding to a molecule on their surface called Ace2.
There is a wide range of approaches to vaccine development; Chadox1 Nov-19 is what is known as a viral vector vaccine. To make this vaccine, particles of another, a harmless virus called Chadox1 are loaded with a portion of SARS-Cov-2 DNA that instructs cells how to build a spike protein.
When these chadox1 particles infect human cells, the DNA of the coronavirus is then "expressed", creating a spike protein for the immune system to respond to. What is important for the safety of the vaccine, the viral vector cannot multiply and cause permanent infection.
The chadox1 viral vector has been used to make eight vaccines already in clinical trials to treat other human diseases, including Middle East respiratory syndrome or MERS, a coronavirus that is linked to Sars-Cov-2.
What will happen now?
Crucially, we must demonstrate that the vaccine is effective — that it results in significantly lower, ideally zero, cases of Covid-19 in the chadox1 nCov-19 vaccinated group compared to the control group. Reducing infection rates in the United Kingdom is an excellent result for the health of the nation, but may compromise the ability to show it.
If there are no cases of Covid-19 in the group that received the control vaccine, then it is pointless to compare this group with the vaccinated group. Deliberately infecting people with the virus may be possible in the future after careful consideration of the ethical consequences, but this is not currently allowed.
For this reason, a second study was launched with about 10,000 people in the UK, focusing on healthcare professionals, and further research is being conducted in Brazil and South Africa, where infection rates are significantly higher. An expanded study in the UK will include children and the elderly to assess the effectiveness of the vaccine in these age groups. Immune responses in people over 70 years of age are often lower than in young people.
It is very important to monitor the vaccine-induced immune response for at least one year to assess whether booster injections will be required, and if so, how often. My personal prediction-based on reduced antibody levels in people infected with other types of coronaviruses, rather than data from the current vaccine trial — is that we will probably need annual boosters like the annual flu shots.
Finally, if the vaccine is effective, it will require the rapid production of potentially billions of doses to supply the entire world. To facilitate this, AstraZeneca has already initiated a large-scale vaccine production program targeting hundreds of millions of doses with delivery starting at the end of 2020.
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