Scientists competing to develop a safe and effective COVID-19 vaccine are turning to what may seem like a strange ally: another family of viruses.
At least five candidate vaccines are built on the backs of adenoviruses, a common family of pathogens that are often used as vehicles to deliver a variety of therapies to human cells. A sixth candidate uses a close relative of the family.
Molecular biologists who develop the vaccine use adenovirus as a type of vehicle to train the human body to identify and block a deadlier pathogen such as coronavirus, not unlike the way a Ford F-350 base can be used. to transport a pill Truck or ambulance.
Scientists start by removing viral proteins from an adenovirus, making it harmless to humans. They then insert DNA sequences from the coronavirus spike protein, the particle that allows the virus to bind and enter a human cell.
“We can take these viruses from the common cold and we can disable them basically so they don’t replicate, so they don’t cause disease,” said Dan Barouch, an immunologist at Harvard Medical School and director of the Center for Virology and Vaccine Research. at the Beth Israel Deaconess Medical Center. “We can link a DNA fragment of a pathogen of interest. In this case, it’s the spike protein COVID-19 “.
Once the adenovirus-based vaccine is administered, the harmless virus enters a human cell, where it begins to reproduce the protein. If everything goes according to plan, the human cell will recognize the invader, the harmless virus with the added protein, and will kill it, generating an immune response.
That process effectively trains the immune system to identify the new protein. If someone who has received a successful vaccine is infected with the SARS-CoV-2 virus, their immune system could identify them and block their entry and reproduction.
Under normal circumstances, adenoviruses are relatively common and relatively low-threat to humans. They can cause minor respiratory infections, such as the common cold. In some rare cases, they can cause more severe symptoms and even death; One strain, adenovirus 7, killed a freshman at the University of Maryland in 2018.
But the adenoviruses used in vaccines become harmless long before they get close to a human.
Adenoviruses are commonly used in the development of vaccines, gene therapy, and even to fight tumors. An Ebola virus vaccine, developed by the US Army Medical Research Institute for Infectious Diseases in Fort Detrick, Maryland, was administered to hundreds of thousands of people in the Democratic Republic of the Congo during an outbreak that ended last month, after two long years.
The adenovirus family lends itself to such work, biologists said, in part because the various species tend to infect many different types of cells within the body. That gives the body’s immune system more opportunities to protect itself against any protection against the vaccine, in this case, the coronavirus. Adenoviruses are also more likely to elicit an immune response after a single dose, while other vaccines require multiple injections.
“It has a good immune response and is generally completely safe in terms of any viral activity that causes disease, because the viral genes are killed,” said William Klimstra, a microbiologist at the University of Pittsburgh Vaccine Research Center. . “We have to evaluate many different candidates because we don’t fully understand what kind of immune response is needed.”
At least three of the most promising vaccine candidates are using different adenovirus species as bases.
Researchers from the University of Oxford and AstraZeneca are using an adenovirus found in chimpanzees called ChAdOx1; They reported this week that the vaccine was safe and produced an immune response, a positive result that gives scientists hope that the first doses can be administered under emergency conditions by October.
A Chinese company called CanSino Biologics is using the Ade5 virus Ad5 in trials with members of the Chinese military. The company said this month that phase two trials showed the vaccine created its own immune response, and the Chinese military approved it for use in special circumstances.
Barouch’s team at Beth Israel Deaconess, in association with Johnson and Johnson, is using Ad26, another adenovirus, as their delivery vehicle. It is the same adenovirus that Johnson and Johnson used to create a second Ebola virus vaccine. Phase two trials are underway, and the teams hope to produce up to a billion doses by next year.
Researchers from the Gamaleya Research Institute in Russia; Swiss pharmaceutical giant Novartis and Massachusetts Eye and Ear Hospital; and the San Francisco-based pharmaceutical company Vaxart are using adenoviruses or close relatives in vaccine candidates who are not yet as advanced in tests and trials.
The substantial number of developing vaccine candidates worldwide is giving hope to scientists who initially worried that developing a SARS-CoV-2 vaccine would take years. Advances in technology are accelerating the process, the researchers said, as new candidates race through the tests.
“Many modern vaccine technologies advance very rapidly. Historically, the entire vaccine company has been mired in the past, ”said Klimstra. “These technologies are actually much more likely to be safer and more effective than older technologies that have been used historically. That is something really positive that is coming out of this bad situation. “
There are many different bases on which to build a vaccine. Moderna, the first US company to begin human trials, has a candidate vaccine that uses messenger RNA to make proteins from SARS-CoV-2. Pfizer is working with the German company BioNTech and a Chinese firm called Fosun Pharma to develop an mRNA vaccine. Inovio and a South Korean company called Genexine are using other DNA-based vaccines. The leading vaccine candidates for Merck use vesicular stomatitis virus and a measles virus as delivery mechanisms.
“I am cautiously optimistic about all of these vaccine technologies,” Barouch said in an interview. “There is a good chance that multiple vaccines will work. It is not really a question of one or the other. “
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