The Efficacy Comparison Between Vaccine Vectors Vaccinia Tian Tan And Modified Vaccinia Virus Ankara In Inducing Protective Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus S Protein

Immunization with a killed or inactivated viral vaccine provides significant protection in animals against challenge with certain corresponding pathogenic coronaviruses (CoVs). However, the promise of this approach in humans is hampered by serious concerns over the risk of leaking live severe acute respiratory syndrome (SARS) viruses. A SARS vaccine candidate was generated by using the live-attenuated modified vaccinia virus Ankara (MVA) as a vector. The full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletion III region of the MVA genome. The newly generated recombinant MVA, SARS-MVA, is replication incompetent in mammalian cells and highly immunogenic in terms of inducing potent neutralizing antibodies in mice, rabbits, and monkeys. After two intramuscular vaccinations with SARS-MVA alone, the 50% inhibitory concentration in serum was achieved with reciprocal sera dilutions of more than 1,000- to 10,000-fold in these animals.However, considering that vaccinia Tian Tan (VTT) was used as a vaccine against smallpox in China for millions of people before 1980, in this study we generated a SARS vaccine candidate by using the VTT as a vector. The full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletionⅢregion of the VTT genome. The newly generated recombinant VTT, SARS-MVTT, as well as SARS-MVA, is well attenuated and highly immunogenic in terms of inducing potent neutralizing antibodies in mice via intramuscularly with 105 and 106 pfu. And there was a clear dose dependency between the four SARS-MVTT and SARS-MVA dosing groups. However, SARS-MVTT, when inoculated via oral and intranasal with 105 and 106 pfu, has great advantage over SARS-MVA in inducing neutralizing antibodies against SARS-Cov S protein:as to SARS-MVTT, the IC50 was achieved when the sera were diluted between 1000 and 10000 fold while the IC50 could hardly be achieved as to SARS -MVA.