Science Back-to-Back . . . Natural immunity or DNA vaccine immunity can provide effective memory immunity protection for rhesus monkey SARS-CoV-2 reinfection.

The covid-19 pandemic has posed a major threat to global public health security. However, we do not know enough about the immune pathogenesis of sars-cov-2, especially the protective immunity assessment of sars-cov-2 infection.on May 20, 2020, the Dan Barouch team of Harvard Medical School published two research papers on science at the same time, namely, sars-cov-2 infection protection against sars-cov-2 in rhesus macaques and DNA vaccine protection against sars-cov-2 in rhesus macaques The natural immunity induced by sars-cov-2 infection and the protection of active immunity induced by DNA vaccine in rhesus monkey model were discussed. It was found that the natural antibody response induced by sars-cov-2 infection in rhesus monkey model could protect the occurrence of repeated infection.in addition, DNA vaccine can also provide protection for rhesus monkeys and effectively prevent sars-cov-2 infection, which can be used as a candidate vaccine for covid-19.the researchers first established a sars-cov-2 infected rhesus monkey model. Nine rhesus monkeys were divided into three groups and inoculated with different doses of virus. A considerable amount of virus load was detected in nasal swab (NS) and bronchoalveolar lavage fluid (BAL), but not in plasma. In addition, all rhesus monkeys also had different degrees of appetite loss, and the high-dose group showed mild However, fever, weight loss and dyspnea were not observed.immunohistochemistry (IHC), in situ RNA hybridization (rnascope) and circulating immunofluorescence (cycif) results showed that sars-cov-2 mainly infected lung cells and bronchial epithelial cells, as well as neutrophil infiltration and interstitial pneumonia symptoms.sars-cov-2 induced acute interstitial pneumonia.it is important that the specific antibody and cellular immune responses of sars-cov-2 were observed in all rhesus monkeys on the 35th day, and the T cell response of the high-dose group was more intense. After the virus was completely eliminated, 9 rhesus monkeys were re immunized with the same dose, and 3 uninfected rhesus monkeys were immunized as controls.the results showed that 5 out of 9 could be free from infection, and the other 4 could detect low viral load, but it quickly dropped below the detection limit.no clinical symptoms were observed in all 9 rhesus monkeys.it is worth noting that the specific antibody response and T cell response were rapidly induced by the secondary immunization in rhesus monkeys, and the antibody titer on the 14th day after the second immunization was significantly higher than that on the 14th day after the first infection.these results suggest that the immune memory of immunized rhesus monkeys shows immune memory, and the immune memory induced by sars-cov-2 infection can provide protective immunity for re infection.this result is also consistent with the previous results of Qin Chuan team, Chinese Academy of Medical Sciences (in the sars-cov-2 infected rhesus monkey model, there is a conjunctival infection pathway, which will not be re infected after rehabilitation).subsequently, the researchers developed a variety of different forms of S protein DNA vaccine (s full length, s.dct, s.dtm, S1, RBD, S dTM.PP ）Thirty five rhesus monkeys were immunized with 5 mg intramuscularly at week 0 and week 3 DNA vaccine, at week 5, it was observed that the vaccine induced neutralizing antibodies to pseudovirus and live virus, including multiple subtypes and different effector functions. S protein specific T cell response (mainly Th1 response) was induced at week 5.at the 6th week, i.e. 3 weeks after the enhanced immunization, all rhesus monkeys were infected with sars-cov-2. Compared with the control group, the other vaccine groups except s.dtm group showed lighter clinical symptoms and lower levels of viral RNA.correlation analysis showed that the protective effect of the vaccine was significantly related to the titer of the antibody. In response to sars-cov-2 infection, neutralizing antibodies play a major role, and some innate immune effectors play an auxiliary role.in conclusion, the researchers first established a sars-cov-2 infected rhesus monkey model, and confirmed that the naturally induced immune response induced by sars-cov-2 infection can effectively protect rhesus monkeys from secondary infection.the antibody level induced by the developed DNA vaccine in rhesus monkey model was similar to that of the convalescent patients, and the protective effect of the vaccine was significantly related to the antibody titer.the most effective full-length s protein DNA vaccine can reduce the viral load of nasal mucosa and bronchoalveolar lavage fluid by thousands of times.these results provide strong support for vaccine research in non-human primates.original address: plate maker: Ke