Virus World

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 get emergency approval in several countries before completing large-scale trials, the Wall Street Journal reported last week. 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. “The Ad5 concerns me just because a lot of people have immunity,” said Anna Durbin, a vaccine researcher at Johns Hopkins University. “I’m not sure what their strategy is … maybe it won’t have 70 percent efficacy. It might have 40 percent efficacy, and that’s better than nothing, until something else comes along.”

Vaccines are seen as essential to ending the pandemic that has claimed over 845,000 lives worldwide. Gamaleya has said its two-virus approach will address Ad5 immunity issues.  Both developers have years of experience and 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 employ harmless viruses as “vectors” to ferry genes from the target virus — in this case the novel coronavirus — into human cells, prompting an immune response to fight the actual 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. Several researchers have chosen alternative adenoviruses or delivery mechanisms. Oxford University and AstraZeneca based their COVID-19 vaccine on a chimpanzee adenovirus, avoiding the Ad5 issue. Johnson & Johnson’s candidate uses Ad26, a comparatively rare strain. Dr. Zhou Xing, from 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, theorizing it could circumvent pre-existing immunity issues. “The Oxford vaccine candidate has quite an advantage” over the injected CanSino vaccine, he said. Xing also worries that high doses of the Ad5 vector in the CanSino vaccine could induce fever, fueling vaccine skepticism.

“I think they will get good immunity in people that 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, about 40 percent of people have high levels of antibodies from prior Ad5 exposure. In Africa, it could be has high as 80 percent, experts said.  Some scientists also worry an Ad5-based vaccine could increase chances of contracting HIV.  In a 2004 trial of a Merck & Co Ad5-based HIV vaccine, people with pre-existing immunity became more, not less, susceptible to the virus that causes AIDS. Researchers, including top U.S. infectious diseases expert Dr. Anthony Fauci, in a 2015 paper, 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 at-risk populations.  Gamaleya’s vaccine will be administered in two doses: The first based on Ad26, similar to J&J’s candidate, and the second on Ad5. Alexander Gintsburg, Gamaleya’s director, has said the two-vector approach addresses the immunity issue. Ertl said it might work well enough in individuals who have been exposed to one of the two adenoviruses.

On Tuesday, Russian President Vladimir Putin announced that his country had registered the world's first coronavirus vaccine, named ‘Sputnik V’. The president said that one of his daughters had tested the vaccine on herself.

What we know about the vaccine:

• Developed by Moscow’s Gamaleya Research Institute of Epidemiology and Microbiology, the dose is based on a platform already used for six other vaccines, according to Russian Minister of Health Mikhail Murashko.
• The Ministry of Health registered ‘Sputnik V’ as a solution to be injected.
• According to the results of clinical studies, the vaccine has shown both high efficacy and safety.
• All the volunteers developed high titers [concentration levels] of antibodies to Covid-19, Murashko noted.
• He also said that “none of them had serious complications” after receiving the vaccine.
• After vaccination, immunity to Covid-19 can last up to two years, the Health Ministry claimed. 

How the vaccine will be distributed:

• President Putin expects that mass production of the coronavirus vaccine will begin in the near future.
• The solution will be produced at two sites: The Russian Ministry of Health’s Gamaleya  Institute and the domestic biopharmaceutical company Binnopharm.
• Some foreign countries have already shown interest in acquiring doses of the Russian vaccine.

Vaccination:

• Medical workers and teachers will be the first to receive the vaccine. 
• Vaccination of medical professionals could begin in late August or September.
• ‘Sputnik V’ will be available to the general public on January 1, 2021.
• Vaccination will be voluntary in Russia.

The Russian Direct Investment Fund and the Gamaleya  Institute of Epidemiology and Microbiology have launched a new website with information about ‘Sputnik V’. 

Despite Putin’s reported endorsement, little-tested vaccine is not approved for widespread use until 2021. In a startling and confusing move, Russia claimed today it had approved the world’s first COVID-19 vaccine, as the nation’s Ministry of Health issued what’s called a registration certificate for a vaccine candidate that has been tested in just 76 people. The certificate allows the vaccine, developed by the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow, to be given to “a small number of citizens from vulnerable groups,” including medical staff and the elderly, a Ministry of Health spokesperson tells ScienceInsider. But the certificate stipulates that the vaccine cannot be used widely until 1 January 2021, presumably after larger clinical trials have been completed. Scientists around the world immediately denounced the certification as premature and inappropriate, as the Gamaleya vaccine has yet to complete a trial that convincingly shows it is safe and effective in a large group of people. Even some within Russia challenged the move. “It's ridiculous,” says Svetlana Zavidova, a lawyer who heads the Association of Clinical Research Organizations in Russia. “I feel only shame for our country.” Zavidova, who has worked on clinical trials for 20 years and anticipated the approval, yesterday sent an appeal to the Ministry of Health to postpone registering the vaccine until proper efficacy trials are completed. “Accelerated registration will no longer make Russia a leader in this race, it will only expose end users of the vaccine, citizens of the country of the Russian Federation, to unnecessary danger,” she wrote on behalf of the clinical research group.

Gamaleya has developed vaccines before, and Mikhail Murashko, the Russian minister of health, said in a government press release that the COVID-19 vaccine showed “high efficacy and safety” and there were no serious side effects. The same release suggested the vaccine would confer 2 years of immunity to SARS-CoV-2, the virus that causes COVID-19. That estimate is apparently based on vaccines Gamaleya has made with similar technology.  Russian President Vladimir Putin reportedly endorsed the use of the vaccine, which is dubbed “Sputnik V,” saying it had “passed all necessary steps” and noting that one of his adult daughters had received it. (Putin has not clearly acknowledged his children in public, but he does sometimes refer to them; one is a medical doctor in Moscow.) Putin, who apparently made these comments at a government meeting, added, “I hope we can start a massive release of this vaccine soon.” 

The Russian registration certificate gives few details about the vaccine, which is being manufactured by Binnopharm in Zelenograd. The company says it can produce 1.5 million doses of the product per year and hopes to expand its manufacturing capacity. More information is available in descriptions of two small trials of the candidate vaccine that appear on ClinicalTrials.gov, a website run by the U.S. National Institutes of Health. The vaccine consists of two shots that use different versions of adenoviruses, some of which cause the common cold, that Gamaleya researchers have engineered to carry the gene for the surface protein, or spike, of SARS-CoV-2. Apparently, the studies are comparing a single shot of adenovirus 26 with the spike gene to a scheme, known as prime-boost, that also gives a second dose 21 days later of a vaccine that contains the spike gene in adenovirus 5.

Some vaccine experts have raised concerns about COVID-19 vaccines that use adenovirus 5 in this way. In 2007, researchers stopped an HIV vaccine trial that used adenovirus 5 to shuttle in the gene for the surface protein of that virus after they found that it increased the likelihood of its transmission. 

In 2017, Gamelaya received approval in Russia for a vaccine that also used the adenovirus 5 vector to deliver the surface protein gene from the virus that causes Ebola. Researchers there used a similar strategy for a vaccine for Middle East respiratory syndrome, a disease caused by a coronavirus like the one responsible for COVID-19. It is still under development and has entered early stage clinical trials.  In the United States, the Food and Drug Administration (FDA) can approve the use of medicines prior to the completion of efficacy trials through what’s known as an emergency use authorization, and there has been growing concern that President Donald Trump will push for this with a COVID-19 vaccine to help his re-election prospects in November. Zavidova says Russia’s certification process is similar to FDA’s emergency use. But FDA has an independent advisory committee, largely consisting of academics, that routinely reviews vaccine approval applications.