Dr. Gertrudis Rojas (Center of Molecular Immunology, Havana, Cuba)
The advent of COVID-19 in Cuba has given rise to an urgent need for effective vaccines in the face of severely limited resources. To meet this challenge, Cuba relies on diversity: multiple production facilities with different platform technologies, multiple vaccine antigen formats, and multiple vaccine candidates. The Soberana family of vaccines are an important component of this complex landscape whose story is written at the interface between biology and chemistry. Their specific antigen component is the virus’s receptor-binding domain—its RBD.
The RBD is a promising vaccine antigen because it’s the part of the main viral surface protein that binds specifically to the receptor protein ACE2 on human cells to initiate infection. People vaccinated with the RBD produce antibodies that can prevent infection by blocking the interaction between the virus’s RBD and the ACE2 receptor on cells in vaccinees’ airways, lungs, and other tissues. A specially engineered form of the RBD was prepared by recombinant DNA technology in mammalian cells—living factories that produce the protein in a natural human-like environment. The RBD was then incorporated into vaccine platforms that had already been developed by Cuba’s extensive vaccination programs, creating three vaccine candidates, Soberana-01, Soberana-02, and Soberna-Plus, that are already being tested and deployed.
Dr. Rojas explained in lay terms how her team in the Protein Engineering lab designed and produced the SARS CoV-2 viral antigen at the heart of three of the five vaccines: Soberana 1, 2, and Plus. The antigen is the so-called receptor-binding domain, or RBD, which is the part of the virus’s Spike surface protein that initiates the infection process by making direct contact with a receptor called ACE2 on the surface of human cells. The Protein Engineering team produced the engineered RBD protein on a laboratory scale to confirm its structure. In particular they showed that it binds ACE2, and used mass spectrometry to demonstrate that the four strong chemical bonds—the “disulfide bridges”—that lock the protein in its natural three-dimensional shape are all intact. They then produced stable lines of Chinese hamster ovary cells that secrete the engineered protein in high yield in culture. Those cell lines have allowed the protein to be produced at industrial scale in huge bioreactors for incorporation into doses for country-wide vaccination.
This lecture is sponsored by the Bisan Center for Research and Development, Scientists for Palestine and the Center for Palestinian Studies of Columbia University