The Faculty of Medicine of the Macau University of Science and Technology led a collaborative team on successful development of a SARS-CoV-2 Vaccine. The study is recently published in the world’s leading scientific journal NATURE

COVID-19 Pneumonia is a global pandemic that has been transmitted mainly from person to person. Since the global outbreak began, there are more than 15 million confirmed cases and nearly 640,000 deaths worldwide as of 25th July. It is an urgent need for an effective SARS-CoV-2 preventive vaccine worldwide. According to WHO data, there are more than 150 candidate COVID-19 vaccines under development all around the world. Although a few vaccine candidates have made progress in clinical trials, there are still many difficulties before they can be mass-produced. Professor Zhang Kang from the Faculty of Medicine of Macau University of Science and Technology, led a collaborative research team together with scientists from many institutions in Mainland and Hong Kong, on development of a COVID-19 vaccine. The paper describing this vaccine entitled " A Vaccine Targeting the RBD of the S protein of SARS-CoV-2 Induces Protective Immunity" is published in Nature, a top international academic journal, on July 29.  In this study, they found that SARS-CoV-2 Spike protein (S protein) receptor-binding domain (RBD) could induce a potent functional antibody response in the immunized mice, rabbits and non-human primates as early as 7 or 14 days after a single dose injection. The sera from the immunized animals blocked RBD binding to ACE2 expressed on the cell surface and neutralized the infection by SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Importantly, the vaccination also provided protection in non-human primates from SARS-CoV-2 challenge in vivo. The elevated RBD-specific antibodies were also found in the sera from patients with COVID-19. Several immune pathways and CD4 T lymphocytes were identified to be involved in the induction of the antibody response. Results indicated that antibodies generated by the vaccinating protein do not block, activate or modulate endogenous ACE2 in the absence of the virus. This study highlights the importance of the RBD domain in the SARS-CoV-2 vaccine design and provides the rationale for the development of a potent protective vaccine through the induction of antibody against RBD domain.

In this study, baculovirus expression system was chosen to express the various protein, mainly considering it is a commercially feasible system and can manufacture the candidate vaccine in the commercial market. This study has evaluated the potential of a candidate vaccine based on the RBD domain of SARS-CoV-2, evaluated the appropriate dosing regime and testing its effect in generating neutralizing activity against SARS-CoV-2 in the recipient animals, and determined the immune pathways involved in the generation of the immune response, so as to provide the groundwork for the design of an effective SARS-CoV-2 preventive vaccine. The paper has pointed out, the vaccine had given a potent and complete protection of vaccinated animals including monkeys. There is no evidence of antibody-dependent enhancement or acceleration of pneumonia in mice or monkeys that received the RBD-vaccinated immune sera developed any evidence of pneumonia.  The recombinant RBD protein vaccine is the best vaccine choice as an immunogen as evidenced by a much higher viral neutralization activity than any other parts of S protein, including the entire extracellular domain protein (ECD), S1-subunit protein (S1), or S2-subunit (S2). It proved that the high level of antibodies induced by the RBD vaccine and the high neutralizing activity as demonstrated in the passive immunization experiments suggested that passive immunization may also play a role in the clinical management of a healthy non-vaccinated subjects post-exposure to SARS-CoV-2. Passive immunization may help sever COVID-19 patients clinically, likely through the reduction of viral load. In addition, the involvement of CD4+ T-cells in the coordinated immune response and the cellular pathways in the humoral response identified in the study indicated the significance of augmenting this immune response in the further studies. The findings have proved the scientific value and practicability of the receptor-binding domain in the study of SARS-CoV-2 preventive vaccine, and pointed out the direction for the future vaccine development.

As the main corresponding author of this paper, Professor Zhang Kang of the Faculty of Medicine of Macau University of Science and Technology said, “Our initial thinking when designing our vaccine in January 2020 was to use the smallest part of S protein so it produces the best vaccine effect but has the least potential side effects such as an antibody-dependent enhancement complication, therefore we painstakingly made several vaccine candidates and tested each of them, and concluded that RBD is the best candidate. In hindsight, that seems obvious now, but back in January 2020, when everyone else was racing ahead with vaccine production, it was a hard decision. We are now glad we did not rush and made the right decision before moving forward.” There are more than one hundred COVID19 vaccines under development in the world, but they are facing arduous challenges in efficacy, side effects and production. As COVID-19 pandemic continues to spread around the world, there is an urgent need for effective vaccines to contain the pandemic. In this study, we demonstrated that recombinant vaccines against Spike protein RBD region can effectively induce a potent immune response in the body with a good safety profile. In addition, the biotechnology method used in creating the recombinant RBD vaccine is mature and feasible in aiding a mass vaccine production. Once it is successful, it will provide a good solution for the global fight against COVID-19. However, the efficacy of the vaccine needs to be evaluated and validated in human clinical trials which will be initiated shortly.