It is self-evident that vaccines are novel coronavirus pneumonia, and scientists all over the world are working hard to develop vaccines.
Recently, the antibody based vaccine research has finally got good news.
On May 6, Chinese scientists first published the animal experimental results of the new coronavirus vaccine in science, a top international academic journal.
It's worth noting that, This is the world's first paper to publish in detail the results of a new-crown vaccine animal experiment, produced by the Chinese team and proved the validation of mice, rats and rhesus monkeysAs early as April 19, the preview version of the paper had been published on Bioscience paper platform biorxiv, and attracted great attention in the industry.
The world's first inactivated vaccine
According to the different treatment methods, the vaccine is divided into five kinds: inactivated vaccine, attenuated live vaccine, recombinant protein vaccine, nucleic acid vaccine, recombinant virus vector vaccine.
The researchers used more conventional inactivated vaccines.
Inactivated vaccine means killing the virus directly and throwing the whole body to the immune system for recognition. such as heating to die hot or soaking in formalin. This is the most classic vaccine type, the advantage is safe and mature, the disadvantage is that the virus is dead after all, causing immunity may not be enough.
The main method is to extract virus strains, after inactivation, injected into mice, rats and rhesus monkeys, to induce neutralizing antibodies on them.
So, what are the results of the specific study?
PICo vaccines may induce more effective antibody responses.
The sars-cov-2 strain was isolated from bronchoalveolar lavage fluid (BALF) of 11 hospitalized patients (including 5 intensive care patients), including 5 from China, 3 from Italy, 1 from Switzerland, 1 from the UK and 1 from Spain.
These 11 samples contain sars-cov-2 strains, which are widely distributed in the system tree constructed from all available sequences and represent the circulating sars-cov-2 population to some extent.
In order to make a comparative study, the researchers selected cn2 strain for purification of inactivated sars-cov-2 vaccine development (Pico vaccine) and 10 other strains (known as cN1, cn3-cn5 and 0s1-0s6) as preclinical challenge strains.
In order to evaluate the immunogenicity of Pico vaccine, different doses of Pico vaccine (0, 1.5 or 3 or 6 pg per dose, 0 PG in normal saline as sham group) were injected on day 0 and day 7, and BALB / c mice (N10) were found to have no inflammation or other adverse reactions.
To the researchers' surprise, they further found that in immunized mice, the number of n-specific IgG induction was 30 fbld lower than that of antibodies against s or RBD,The researchers also said that although this observation does not currently show the ability of Pico vaccine to produce similar results in humans, it highlights the potential of Pico vaccine to induce strong and effective immune responses. To sum up,The researchers believe that antibodies against sars-cov-2n can not provide protective immunity against infection, indicating that Pico vaccine may be able to cause more effective antibody response.
The vaccine is safe and effective
Next, the researchers measured the content of sars-cov-2 specific neutralizing antibody in a period of time with mn50. Similar to the s-specific IgG reaction, the neutralizing antibody titer of anti cN1 strain appeared in the first week (high dose immunization 12), and increased sharply after the second week of booster, with the low dose and medium dose reaching about 1500 and the high dose reaching 3000 respectively.
In addition, the immunogenicity evaluation of Pico vaccine on Wistar rats with the same immune strategy showed similar results. After neutralization test on other 9 strains of sars-cov-2 with mouse and rat serum collected 3 weeks after vaccination, the researchers found that Pico vaccine can stimulate antibodies, which may show the same immunogenicity to strains of sars-cov-2 circulating all over the world Effective neutralization activity.
Subsequently, the researchers conducted an experiment to evaluate the immunogenicity and protective effects of the vaccine in rhesus monkeys after vaccination. The researchers gave rhesus monkeys different doses of vaccine on days 0,7 and 14. The results showed that at week 2, S protein-specific IgG and neutralizing antibodies could be induced, and the virus was attacked on day 22 after vaccination.The results showed that compared with the control group, the pathological changes in lung tissue of rhesus monkeys immunized with the vaccine were significantly reduced, and the viral load was also significantly reduced. On the 7th day after infection, no virus was detected in throat, anus and lungs, and no antibody dependent enhancement was observed.
In order to further prove the results of the study, the researchers also verified the safety of the vaccine by observing clinical indicators and biochemical indexes. No fever and weight loss were found in all monkeys vaccinated, and appetite and mental state remained normal. On the 29th day, the pathological evaluation of lung, heart, spleen, liver, kidney and brain showed that picovacc did not cause significant pathological characteristics,The above results show that picovacc is safe in rhesus monkeys.
And there's a worry
Besides proving the vaccine safe, the published study also answers another concern about whether will have ADE effects after vaccination.
ADE effect, that is, antibody-dependent enhancement, refers to the formation of antibodies against the virus that should have been injected into the vaccine, but for some reasons it becomes infectious enhancement of the virus, become a virus
Lei feng.com learned that in 2019, Professor Yuan Guoyong's team published a study on SARS CoV infection and vaccine trial using Chinese macaques. The vaccine eventually produced ade effect. The lung injury caused by infection in macaques using the vaccine was more serious than that in the control group.
But in a recent paper on animal test results,No ade effect was observed in the vaccine. But we can not exclude the possibility of ADE expression after the antibody titer is weakened.Therefore, it is necessary to carry out further research, including observing the challenged animals for a long time after vaccination.
Novel coronavirus pneumonia, which is not able to identify the best animal model of SARS-CoV-2 infection in the study, is also a new animal model. The Ganges RIver monkey, which produces new crown pneumonia symptoms after SARS-CoV-2 infection, seems to be a more suitable animal model for studying the disease. These results provide a way for the clinical application of SARS-CoV-2 vaccine for human beings.
It should be noted that although the vaccine research of Qinchuan team has only published the complete data and results of animal experiments in the form of papers, in fact, the research and development progress of the vaccine has already entered the clinical research stage.
What do experts think?
As early as April 19, when the preview paper was released, it attracted the attention of the industry, and experts and scholars also expressed their views.
Florian krammer, a virologist at the Icahn School of medicine in Mount Sinai, said he liked the data and thoughtTraditional methods, though not novel, can work. Many less developed countries can still make vaccines.
But Professor Douglas reed of the University of Pittsburgh points out:The number of animals in the study is too small to see statistically significant differences. In addition, after infection with the new coronavirus, the symptoms of monkeys are generally lighter than that of humans, so it is impossible to fully simulate human infection.
Mark, an immunologist at Oregon Health and Science Universitythis provides strong evidence that the virus does not mutate and does not develop resistance to # COVID19 vaccines. This is welcome news
Although there is no absolute turning point in the fight against the new crown, all researchers around the world are working hard for it. We just need to be patient and wait for more good news. After all, what can't beat us will make us strong.
Hope the vaccine can be put into clinical use as soon as possible!