Yesterday, the world-renowned academic journal "Science" published on its official website an article titled "Rapid development of an inactivated vaccine candidate for SARS-CoV-2 (the official name of the novel coronavirus)." The article was submitted by academicians conducting a research led by the Qinchuan team of the Chinese Academy of Medical Sciences’s Institute of Laboratory Animal Sciences (ILAS).
This is the first publicly reported result of the study of animal experiments on SARS-CoV-2 vaccine. Prior to this, a preview version of the paper was published on bioRxiv, a preprint repository platform for the biological sciences. The results of animal experiments show that the vaccine developed by Beijing Kexing Zhongwei Biotechnology Co., Ltd., a subsidiary of Kexing Holdings, is safe and effective.
The researchers isolated multiple SARS-CoV-2 strains from the bronchoalveolar lavage fluid (BALF) samples of 11 hospitalized patients (including 5 patients in intensive care), among them, 5 are from China, 3 from Italy, 1 from Switzerland, 1 from the UK and 1 from Spain. The 11 samples contained SARS-CoV-2 strains that are widely scattered on the phylogenic tree constructed from all available sequences, representing, to some extent, circulating SARS-CoV-2 populations .
On this basis, the researchers chose CN2 strain for purified inactivated SARS-CoV-2 virus vaccine development (PiCoVacc) and another 10 strains (termed as CN1, CN3-CN5 and OS1-OS6) as preclinical challenge strains. The vaccine can trigger the production of virus specific neutralizing antibodies in mice, rats and non-human primates. These antibodies effectively neutralize the other 10 selected novel coronavirus strains (CN1, CN3-CN5, and OS1-OS6), indicating that they have potential for neutralizing SARS-CoV-2 strains that are widely circulating worldwide.
The researchers did not observe inflammation or other adverse reactions after injecting the mice with different doses of the vaccine at days 0 and 7 respectively. SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated mice and peaked at the titer of 819,200 (>200 μg/ml) and 409,600 (>100 μg/ml), respectively, at week 6. RBD-specific IgG accounts for half of the S-induced antibody responses, suggesting RBD is the dominant immunogen, which closely matches the serological profile of the blood of recovered COVID-19 patients.
The researchers then evaluated the immunogenicity and protective efficacy of PiCoVacc in rhesus macaques (Macaca mulatta), a non-human primate species that shows a COVID-19-like disease caused by SARS-CoV-2 infection. They immunized rhesus monkeys with different doses (3 μg and 6 μg) of vaccines at day 0, 7, and 14. The results showed that S-specific IgG and NAB (immunoglobulins and neutralizing antibodies) were induced at week 2 , And continued to increase in the third week, the antibody titer is similar to the antibody titer of the recovered Covid-19 patients.
Subsequently, the researchers conducted a challenge study by directly inoculation of the live virus on the 22nd day after immunization. The results showed that compared with the control group (not immunized), the pathological changes of the lung tissue of the rhesus monkey after the vaccine immunization were significantly reduced, and the viral load was also significantly reduced.
On the 7th day after infection of the 4 rhesus monkeys in the high-dose group, no virus was detected in the pharynx, crissum and lung. Viruses were partially detected in pharynx, crissum, and lung specimens on the 7th day after infection in the medium-dose group, but the viral load was reduced by approximately 95% compared with the control group. The results show that 6-microgram dose of candidate vaccine can provide complete protection against SARS-CoV-2, and the 3-microgram dose of vaccine has partial protection.
Researchers have also verified the safety of the vaccine by observing clinical indicators and biochemical indexes. Neither fever nor weight loss was observed in any macaque after the immunization of PiCoVacc, and the appetite and mental state of all animals remained normal.
Hematological and biochemical analysis, including biochemical blood test, lymphocyte subset percent (CD3+, CD4+ and CD8+) and key cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-5 and IL-6) showed no notable changes in vaccinated groups when compared to the sham and placebo groups.
In addition, histopathological evaluations of various organs, including lung, heart, spleen, liver, kidney and brain, from the 4 groups at day 29 demonstrated that PiCoVacc did not cause any notable pathology in macaques
Source: https://science.sciencemag.org/content/early/2020/05/05/science.abc1932.full