Scientists racing to develop a safe and effective COVID-19 vaccine are turning to what may seem like an odd ally: another family of viruses.
At least five vaccine candidates are built on the backs of adenoviruses, a common family of pathogens that are often used as vehicles for delivering a variety of therapies to human cells. A sixth candidate uses a near relative of the family.
Molecular biologists developing the vaccine use the adenovirus as a kind of vehicle for training the human body to identify and block a more deadly pathogen like the coronavirus — not unlike the way the base of a Ford F-350 can be used to carry either a pickup truck or an ambulance.
Scientists begin by removing an adenovirus’s viral proteins, rendering it harmless to humans. They then insert DNA sequences from the coronavirus’s spike protein, the particle that allows the virus to bind to and enter a human cell.
“We can take these common cold viruses and we can deactivate 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 Beth Israel Deaconess Medical Center. “We can stitch in a piece of DNA from a pathogen of interest. In this case it’s the COVID-19 spike protein.”
Once the adenovirus-based vaccine is administered, the harmless virus enters a human cell, where it begins to reproduce the protein. If all goes according to plan, the human cell will recognize the invader — the harmless virus with the added protein — and 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 would be able to identify it and block it from entering and reproducing.
In normal circumstances, adenoviruses are both relatively common and relatively unthreatening to humans. They might cause minor respiratory infections, like the common cold. In some rare cases, they can cause more serious symptoms and even death; one strain, adenovirus 7, killed a freshman at the University of Maryland in 2018.
But the adenoviruses used in vaccines are rendered harmless long before they ever get near a human.
Adenoviruses are commonly used in vaccine development, gene therapies and even to fight tumors. A vaccine against the Ebola virus, developed by the U.S. Army Medical Research Institute for Infectious Disease at Fort Detrick, Md., 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 a lot of different types of cells within the body. That gives the body’s immune system more chances to ward off whatever the vaccine protects against — in this case, the coronavirus. Adenoviruses are also more likely to provoke an immune response after only a single dose, while some other vaccines require multiple injections.
“It makes a good immune response and it’s generally completely safe in terms of any virus disease causing activity, because the viral genes are taken out of it,” said William Klimstra, a microbiologist at the University of Pittsburgh’s Center for Vaccine Research. “Many different candidates need to be tested 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 at 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 that it produced an immune response, a positive outcome that gives scientists hope that the first doses may be delivered under emergency conditions by October.
A Chinese company called CanSino Biologics is using the adenovirus Ad5 in trials on 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 has approved it for use under special circumstances.
Barouch’s team at Beth Israel Deaconess, in partnership with Johnson and Johnson, is using Ad26, another adenovirus, as its delivery vehicle. It is the same adenovirus Johnson and Johnson used to create a second vaccine against the Ebola virus. Phase two trials are underway, and the teams hope to produce as many as a billion doses by next year.
Researchers at the Gamaleya Research Institute in Russia; the Swiss pharmaceutical giant Novartis and the Massachusetts Eye and Ear Hospital; and the San Francisco-based pharmaceutical company Vaxart are all using adenoviruses or near relatives in vaccine candidates that are not yet as far along in testing and trials.
The substantial number of vaccine candidates in development across the world is giving hope to scientists who initially worried that developing a vaccine against SARS-CoV-2 would take years. Advances in technology are speeding the process, researchers said, as new candidates race through trials.
“A lot of modern vaccine technologies are moving forward very rapidly. The whole vaccine enterprise has historically been mired in the past,” Klimstra said. “These technologies are actually much likelier to be safer and to be more effective than the older technologies that had historically been used. That is a real positive that is coming out of this bad situation.”
There are plenty of different foundations on which to build a vaccine. Moderna, the first U.S. firm to begin human trials, has a vaccine candidate that uses messenger RNA to produce 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 each using other DNA-based vaccines. Merck’s leading vaccine candidates use vesicular stomatitis viruses and a measles virus as delivery mechanisms.
“I’m cautiously optimistic about all of these vaccine technologies,” Barouch said in an interview. “There’s a pretty good chance that multiple vaccines may work. It’s not really a question of one or another.”