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Researchers Report Inactivated COVID-19 Vaccine Confers Protection in Monkeys
By Prafull Kumar Singh, D.V.M., Ph.D.
The communication of positive results observed in rhesus macaques is the world’s first report on coronavirus vaccine trials conducted in non-human primates.
Sinovac Biotech Ltd., a China-based biopharmaceutical company, recently announced the publication of preclinical results of its β-propiolactone inactivated SARS-CoV-2 vaccine, PiCoVacc. The vaccine conferred complete protection against SARS-CoV-2 in rhesus macaques and also elicited robust immune responses in mice and rats in a dose-dependent manner. Researchers also noted that PiCoVacc, unlike previous SARS and MERS vaccine candidates do not elicit excessive T-cell responses mediated immunopathology or antibody-dependent enhancement of infection (ADE) even at low titers of neutralizing antibodies in monkeys.
The findings of the preclinical trial are published in the journal Science. The vaccine is already in phase I clinical trials in China to assess the immunogenicity and safety in 144 healthy volunteers aged 18-59 years. Sinovac was also working on the development of a SARS vaccine in 2003; however, the project was abandoned due to a lack of cases.
PiCoVacc was developed by inactivating a SARS-CoV-2 strain isolated from the bronchoalveolar lavage fluid of a patient in China. Ten other circulating SARS-CoV-2 strains were isolated from different parts of the world, including three patients in China, four from Italy and one each from the UK, Switzerland, and Spain. These strains were used to test the immunogenicity of the PiCoVacc in mice and rats and for challenge studies in monkeys.
Vero cell line adapted virus was used to produce the vaccine at large scale. Genomic stability of the adapted virus was assessed by comparing the sequence of the virus isolated from Vero cells at different passages. Comparative genomics detected two mutations between Passage-1, -5, and -10 virus affecting the envelope structural protein (E-A32D) and non-structural protein 10 (nsp10-T32I). No mutations were detected in the spike (S) protein-encoding region, which is a major antigen that induces potent neutralizing antibodies.
PiCoVacc elicited a robust immunoglobulin G (IgG) mediated response against S and receptor-binding domain (RBD; a subdomain within the S1B domain of spike protein) antigens in both BALB/c mice and Wistar rats. Immune responses against the nucleocapsid structural protein, however, were 30 fold lower than S or RBD IgG titers in mice. Serum from vaccinated rats and mice could potently neutralize all the ten clinical isolates of SARS-CoV-2 from five different countries.
The monkeys that received a high dose (n=4) of vaccine had no detectable viral load in pharynx or lung, while the medium-dose group (n=4) showed a 95% reduction in the viral load as compared to the sham group.
Although the findings of the study are promising, they do have lacunae. Firstly, monkeys are not the perfect model for SARS-CoV-2 as they do not develop severe symptoms, as seen in critically ill humans. Moreover, the number of animals per group (4) is too small to apply rigorous statistical testing methods.
Nonetheless, the study provided sufficient evidence that the virus is not mutating rapidly, and vaccines or monoclonal antibodies targeting S protein might provide protection against COVID-19.
“Our study shows that our inactivated vaccine candidate induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and non-human primates, specifically the rhesus macaque. In fact, the results showed that our vaccine candidate offered safe and complete protection in rhesus macaques against SARS- CoV-2 strains,” commented Mr. Weidong Yin, Chairman, President, and CEO of Sinovac.
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