For the first time, one of many developing Covid-19 vaccines has protected an animal, i rhesus macaques, from the infection of the new coronavirus, scientists report. The vaccine, an "old-fashioned" formulation made with a chemically inactivated version of the virus, has not produced evident side effects in monkeys and for this reason human studies have already started on April 16th.
Sinovac Biotech researchers, private company based in Beijing, administered two different doses of their coronavirus vaccine to a total of eight monkeys rhesus macaques. Three weeks later, the team introduced SARS-CoV-2, the virus that causes Covid-19, to monkeys' lungs through tubes in their tracheae, and no one developed a full-blown infection.
Monkeys given the highest dose of vaccine had the best response: seven days after the animals received the virus, the researchers were unable to detect it in the pharynx or lungs of any of them. Some of the low-dose animals had a short "viral blip" but also appear to have controlled the infection, reports the Sinovac team in an article published on April 19 on the bioRxiv prepress server.
In contrast, four control animals developed high levels of viral RNA in different parts of the body and severe pneumonia.
"The results give us a lot of confidence" that the vaccine will work in humans, he says Meng Weining, senior director of Sinovac.
There are those who rejoice ...
He applauds (prudently) the news Florian Krammer, virologist from the Icahn School of Medicine of Mount Sinai, co-author of a report on the status of the numerous vaccines at Covid-19 in development. “This is old school but it may work. What I like most is that many vaccine manufacturers, even in low-middle income countries, could develop a vaccine like this. "
... And who brakes
Douglas Reed University of Pittsburgh, which is developing and testing COVID-19 vaccines in monkey studies, says the number of animals is still too small to produce statistically significant results.
Another concern is that monkeys do not develop the more severe symptoms that SARS-CoV-2 causes in humans. Sinovac researchers recognize in the document that "It is still too early to define the best animal model for the study of SARS-CoV-2", but have noticed that i rhesus macaques not vaccinated, received the virus "They have symptoms very similar to those of Covid-19."
The study also addressed concerns that partial protection could be dangerous. Previous animal experiments with coronavirus vaccines that cause SARS and MERS had found that low antibody levels could worsen. The Sinovac team found no evidence of lung injury in vaccinated animals that produced relatively low levels of antibodies. However, more investigation is still needed.
And the mutations?
SARS-CoV-2 appears to be changing slowly. Yet even so variants could pose a challenge for a vaccine. In test-tube experiments, Sinovac researchers mixed antibodies from monkeys, rats and mice vaccinated with virus strains isolated from Covid-19 patients in China, Italy, Switzerland, Spain and the United Kingdom.
The antibodies have potentially "neutralized" all the strains, "widely scattered on the phylogenetic tree", the researchers observed. This could make the spectrum of the vaccine effective also against the expected mutations of the virus.
"This provides clear evidence that the virus is not mutating in a way that would make it resistant to vaccines.", tweeted the immunologist Mark Slifka of Oregon Health & Science University.
Sinovac, a vaccine factory
Sinovac has marketed inactivated viral vaccines for foot-and-mouth disease, hepatitis A and B and H5N1 or avian influenza. Meng says it could produce around 100 million doses of the vaccine. It may be necessary to work with other manufacturers if the company's vaccine proves safe and effective in human trials.
The company recently launched Phase I clinical trials in Jiangsu province, north of Shanghai, which aim to assess safety and immune responses in 144 volunteers. An equal number of participants will receive high and low doses or a placebo.
Although placebos are not generally used in phase I studies, which do not evaluate efficacy, Meng says that this can help better assess whether the vaccine causes dangerous side effects.
The company hopes to start phase II studies by mid-May: same formulation but administered to more than 1000 people, with results expected by the end of June.
If all goes well, says Meng, Sinovac will try to launch traditional Phase III efficacy studies that compare the vaccine with a placebo in thousands of people.
To quickly obtain additional efficacy data after phase I and II studies and potentially help people, Meng says Sinovac could seek regulatory authorization in China and other countries for emergency authorization to give those who are vaccinated high risk of infection, such as customs officers and police officers.
In Congo in 2018, he began to widely use an experimental Ebola vaccine with this status and evidence suggests that it helped powerfully curb that outbreak. (That Ebola vaccine received regulatory approval for the first time in November 2019).
The situation of vaccines in the world
According to the WHO, another 6 vaccines have entered human studies since April 23 and another 77 are in development. The vast majority of these vaccines use genetic engineering tools (only 4 are based on the "old" inactivation technology) but Meng says that what ultimately matters is whether a vaccine is safe and effective, not how it is made.