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TORONTO: The high-profile COVID-19 vaccines developed in Russia and China share a potential shortcoming: They are based on a common cold virus that many people have been exposed to, potentially limiting their effectiveness, some experts say.
CanSino Biologics’ vaccine, approved for military use in China, is a modified form of adenovirus type 5 or Ad5. The company is in talks to gain emergency approval in several countries before completing large-scale tests, the Wall Street Journal reported last week.
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A vaccine developed by Moscow’s Gamaleya Institute, approved in Russia earlier this month despite limited testing, is based on Ad5 and a second less common adenovirus.
“Ad5 worries me just because a lot of people have immunity,” said Anna Durbin, a vaccine researcher at Johns Hopkins University. “I’m not sure what your strategy is … it might not be 70 percent effective. It could be 40 percent effective, and that’s better than nothing, until something else comes along.”
Vaccines are considered essential to end the pandemic that has claimed more than 845,000 lives worldwide. Gamaleya has said that her two-virus approach will address Ad5 immunity issues.
Both developers have years of experience and have approved Ad5-based Ebola vaccines. Neither CanSino nor Gamaleya responded to requests for comment.
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Researchers have experimented with Ad5-based vaccines against a variety of infections for decades, but none are widely used. They use harmless viruses as “vectors” to transport genes from the target virus, in this case the coronavirus, into human cells, triggering an immune response to fight the real virus.
But many people already have antibodies against Ad5, which could cause the immune system to attack the vector instead of responding to the coronavirus, making these vaccines less effective.
Various investigators have chosen adenovirus or alternative delivery mechanisms. The University of Oxford and AstraZeneca based their COVID-19 vaccine on a chimpanzee adenovirus, avoiding the Ad5 problem. The Johnson & Johnson candidate uses Ad26, a relatively rare strain.
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Dr. Zhou Xing of Canada’s McMaster University worked with CanSino on its first Ad5-based vaccine, for tuberculosis, in 2011. His team is developing an inhaled Ad5 COVID-19 vaccine, with the theory that it could avoid pre-existing immunity problems.
“The Oxford vaccine candidate has a huge advantage” over the injected CanSino vaccine, he said.
Xing is also concerned that high doses of the Ad5 vector in the CanSino vaccine could induce fever, fueling skepticism of the vaccine.
“I think they will get good immunity in people who don’t have antibodies to the vaccine, but a lot of people do,” said Dr. Hildegund Ertl, director of the Vaccine Center at the Wistar Institute in Philadelphia.
In China and the United States, about 40 percent of people have high levels of antibodies from previous exposure to Ad5. In Africa, it could be as high as 80 percent, experts said.
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HIV RISK
Some scientists are also concerned that an Ad5-based vaccine may increase the chances of contracting HIV.
In a 2004 trial of a Merck Ad5-based HIV vaccine, people with pre-existing immunity became more, not less, susceptible to the virus that causes AIDS.
Researchers, including America’s leading infectious disease expert Dr. Anthony Fauci, said in a 2015 article that the side effect was likely unique to HIV vaccines. But they cautioned that HIV incidence should be monitored during and after trials of all Ad5-based vaccines in at-risk populations.
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“I would be concerned about the use of those vaccines in any country or any population that is at risk of contracting HIV, and I put our country as one of them,” said Dr. Larry Corey, co-director of the Vaccine Prevention Network. the US Coronavirus, who was the principal investigator of the Merck trial.
The Gamaleya vaccine will be administered in two doses: the first based on Ad26, similar to the Johnson & Johnson candidate, and the second on Ad5.
Alexander Gintsburg, director of Gamaleya, has said that the two-vector approach addresses the problem of immunity. Ertl said it could work quite well in people who have been exposed to one of the two adenoviruses.
Many experts expressed skepticism about the Russian vaccine after the government declared its intention to administer it to high-risk groups in October without data from large pivotal trials.
“Demonstrating the safety and efficacy of a vaccine is very important,” said Dr. Dan Barouch, a Harvard vaccine researcher who helped design the Johnson & Johnson COVID-19 vaccine. Often, he noted, large-scale trials “do not give the expected or required result.”
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