AZD1222, developed by the University of Oxford and licensed for AstraZeneca, was one of the first vaccines created to protect against COVID-19. A non-replicative viral vector vaccine that was approved for emergency use in several countries was later discontinued due to links to the formation of harmful blood clots. While clinical trials and authorization procedures gained significant media coverage, less was said about the pioneering generation AZD1222, a modified chimpanzee adenovirus called ChAdOx1.
viral delivery
Viruses hijack inflamed cells and force them to produce copies of the virus itself. Scientists have long exploited this ability to create “viral vector” vaccines that do not replicate, in which a virus is genetically modified to decrease its pathogenicity while inducing cells to produce the immunogenic. proteins from some other virus. This approach exposes a host’s immune formula for expressing proteins from a target virus, but not the virus itself, allowing the host to safely expand immunity. In the case of AZD1222, this protein is the spike protein of SARS-CoV-2, the virus that causes COVID-19.
In 2012, researchers at the University of Oxford created ChAdOx1, a viral vector vaccine based on a modified ape adenovirus. The researchers chose an ape adenovirus because “if you use a human adenovirus to immunize humans, you face the challenge of immunity,” says Sarah Gilbert, a professor of vaccinology at the University of Oxford and co-founder of Vaccitech, which patented the ChAdOx1 technology. After successful collaborations with other establishments of other adenovirus apes, Gilbert says, “We looked for ours. We checked for a chimpanzee virus that had been described in the literature, and then a student in the lab turned it into a vaccine vector,” and ChAdOx1 was born.
To create the platform, Gilbert’s team changed the viral genome to eliminate its ability to mirror and optimize its manufacturing. They can then insert the gene encoding a desired viral protein. The end result is an injectable solution that infects the cells around the injection and causes a much higher expression of the target protein. In the case of AZD1222, “something like 80% of the protein expressed by the adenovirus is a spike protein,” Gilbert says.
The host’s immune formula learns to recognize and respond to the expressed protein, but since the virus cannot create new copies of itself, the short-lived infection does not proliferate in the frame and does not cause disease. This makes the platform very useful, even in other people with weakened immune formulas, Gilbert says. “It’s like I have a coronavirus infection in my arm, but it’s not a coronavirus, it’s the adenovirus and it can’t replicate. “
ChAdOx1 as a platform that a product
Gilbert describes modified ape adenovirus as a “real-generation platform” that can be modified to cause the expression of other viral proteins without any alteration in production or safety. The Oxford researchers are their platform to examine vaccines opposed to many diseases, such as tuberculosis, rabies, MERS, dengue and Zika virus.
Ahmed Salman, a vaccinologist and senior immunologist at the University of Oxford, adds that ChAdOx1-based vaccines are simple to produce and solid once manufactured, and says gigantic amounts can be produced “with a very low load in a short period of time. “The platform is also very effective at inducing a strong B-cell and T-cell response, while competing technologies generate a biased response.
At the KAIMRC convention “COVID-19 Vaccines: Global Challenges
Vaccine skeptics that such immediate progression means those therapies will have to be misunderstood or misproven. Salman argues that vaccine studies are usually hampered by slow bureaucratic processes and wasted time waiting for grants, approvals, and publication, all while other people suffer from illness. With COVID-19, he says, we have a “good example” that things can be simplified further. “I think about malaria, which doesn’t get [the same attention as COVID-19]. We will be in clinical trials in a few weeks, but we started the studies more than seven years ago.
In addition, vaccines such as AZD1222 were not created from scratch for COVID-19; rather, they build on decades of existing studies. Scientists also didn’t have to face the pandemic blindly: it was planned. In 2016, says Salman, the University of Oxford presented its “Pandemic X” project. Scientists have prepared plans based on the expectation of diseases. that can cause a global pandemic, treatments that can help, and infrastructure that will be put in place to mitigate disasters. Salman adds that there have been many regional outbreaks since 2000, such as swine flu, bird flu, SARS, MERS, Zika and Ebola. , who have submitted preparation classes. In this context, it is clear that the global network of studies will have to continue to prepare for what can follow.
Building for the future
For Gilbert and Salman, the problems did not prevent the deployment of the Oxford/AstraZeneca vaccine. “We’re busy,” Gilbert says, adding that testing is ongoing. Researchers will stick to trial participants six months and one year later. your dose at the moment to collect blood samples and generate long-term data. Gilbert and his team have expanded their studies to include a cohort of other HIV-positive people in the UK and South Africa. However, many of those trials have been halted due to fears that the vaccine could cause harmful blood clots in rare cases.
Concerns arose after the vaccine’s launch, when several countries reported that it appears to be linked to harmful blood clots in very rare cases. Despite the shortage, this led some regulators to temporarily suspend the use of the vaccine and then only allow its use. through certain groups, such as the elderly. In general, the consensus among fitness officials is that the benefits outweigh the risks, but studies are being conducted on the mechanism behind clotting in the hope that this will further reduce the risks, while aiding expert evaluation.
“So far we’ve gotten approval in 15 countries, but there are other regulators who are still doing their testing and submitting questions that we want to answer very quickly,” Gilbert says. “And once I have time to do anything else, I have all the other vaccine projects I worked on last year. “