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 get emergency approval in several countries before completing large-scale trials, the Wall Street Journal reported last week.
A vaccine developed by the Gamaleya Institute in Moscow, approved in Russia earlier this month despite limited testing, is based on Ad5 and a second, less common adenovirus.
“The announcement5 worries me just because a lot of people are immune,” said Anna Durbin, vaccine researcher at Johns Hopkins University. “I don’t know what their strategy is… maybe it won’t be 70% effective. It can be 40% efficient, and it’s better than nothing, until something else happens. ”
Vaccines are considered essential to end the pandemic that has claimed more than 845,000 lives worldwide. Gamaleya said his two-virus approach would solve Ad5 immunity issues.
Both developers have years of experience and have approved Ebola vaccines based on Ad5. Neither CanSino nor Gamaleya responded to requests for comment.
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 the genes of the target virus – in this case, the novel coronavirus – into human cells, eliciting an immune response to fight the actual virus.
But many people already have antibodies to Ad5, which could cause the immune system to attack the vector instead of responding to the coronavirus, making these vaccines less effective.
Several researchers have chosen alternative adenoviruses or delivery mechanisms. The University of Oxford and AstraZeneca based their COVID-19 vaccine on a chimpanzee adenovirus, thus avoiding the problem of Ad5. The Johnson & Johnson candidate uses Ad26, a relatively rare strain.
Dr. Zhou Xing of McMaster University in Canada worked with CanSino on its first Ad5-based vaccine against tuberculosis in 2011. His team is developing an inhaled Ad5 COVID-19 vaccine, theorizing that it could bypass pre-existing immunity issues.
“The Oxford vaccine candidate has quite an advantage” over the injected CanSino vaccine, he said.
Xing is also concerned that large doses of the Ad5 vector in the CanSino vaccine could cause fever, fueling skepticism about the vaccine.
“I think they’ll 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 Wistar Institute Vaccine Center in Philadelphia.
In China and the United States, around 40% of people have elevated levels of antibodies from previous exposure to Ad5. In Africa, it could reach 80%, according to experts.
Some scientists are also concerned that an Ad5 vaccine will increase the chances of contracting HIV.
In a 2004 trial of an HIV vaccine based on Merck & Co Ad5, people with pre-existing immunity became more susceptible to the virus that causes AIDS, not less.
Researchers, including American infectious disease specialist Dr Anthony Fauci, in a 2015 article, said 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 populations at risk.
“I would be concerned about the use of these vaccines in any country or population at risk of contracting HIV, and I place our country as one of them,” said Dr Larry Corey, co- leader of the US Coronavirus Vaccine Prevention. Network, who was a principal investigator on the Merck trial.
Gamaleya’s vaccine will be administered in two doses: the first based on Ad26, similar to the J&J candidate, and the second on Ad5.
Alexander Gintsburg, director of Gamaleya, said the two-vector approach solves the problem of immunity. Ertl said it might work quite well in people who have been exposed to one of the two adenoviruses.
Many experts have expressed skepticism about the Russian vaccine after the government said it intended to give it to high-risk groups in October without data from large pivotal trials.
“It is very important to demonstrate the safety and efficacy of a vaccine,” said Dr. Dan Barouch, a Harvard vaccine researcher who helped design J & J’s COVID-19 vaccine. Often, he noted, large-scale trials “do not deliver the desired or required result”.
Additional reporting by Christine Soares in New York, Kate Kelland in London, Polina Ivanova in Moscow and Roxanne Liu in Beijing; Editing by Caroline Humer and Bill Berkrot
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