Soberana 02 and Abdala: World’s first Protein conjugate Vaccines against COVID-19

The technology used by Cuba to develop protein-based vaccines against COVID-19 can lead to development of vaccines against new mutated strains in a relatively easier manner. World’s first protein conjugate vaccines have been developed by exploiting the RBD (receptor binding domain) region of the spike protein, responsible for entry of virus into human cells. Apart from other advantages such as stability at 2-8° C, well proven technology, these protein-based vaccines can be relatively easily tailored to make new vaccines against the mutated strains by producing the mutant RBDs. These mutant RBDs can be used as vaccine candidates specific for high-risk strains such as the one recently identified, named Omicron and any other potential strains of the SARS-CoV-2 virus. 

The havoc created by COVID-19 around the world, leading to over 5 million deaths and over 26 million cases, has prompted the researchers and regulatory authorities to introduce emergency use vaccination to protect the human population. A number of DNA based (Covishield, Sputnik V etc.) and mRNA based (by Pfizer and Moderna) have been administered to people to negate the effects of COVID-19 disease. Vaccine based on the use of entire attenuated virus (Covaxin/Sinovac) has also been approved and exported to various countries across the world. Use of proteins and/or protein sub-units is another way of developing vaccines by introducing a recombinant protein in the body to elicit an immune response1. The protein may be conjugated to a polysaccharide or another protein from an unrelated organism in order to boost the immune response. The advantage of protein and protein sub-unit-based vaccines are that the technology is well-established and proven, relatively stable at 2-8° C, absence of live viral DNA or RNA, hence no risk of causing disease and are suitable for people with compromised immune systems. However, protein-based vaccines mainly only trigger antibody responses which may be weak at times, and hence adjuvants and booster doses might be required to increase their efficacy. 

In this article, we describe the development of Soberana 02 and Abdala, world’ first protein conjugate vaccines developed by Cuba. Both the vaccines were greater than 90% effective after three doses2. Soberana 02 vaccine consists of recombinant RBD (receptor binding domain) of the spike protein of SARS-CoV-2 virus conjugated to tetanus toxoid3. The RBD has been produced in mammalian cells4. Two doses of Soberana 02 were safe and attained an efficacy of 71% in adult population aged 19-80 years, while administration of a third does increased the efficacy to 92.4%3. The third dose was however, a heterologous vaccine called Soberana Plus that consisted of a RBD dimer alone. The vaccine demonstrated high immunogenicity, development of RBD neutralizing antibodies and elicited a specific T cell response. In case of Abdala vaccine, the RBD has been produced in yeast (Pichia pastoris) and this vaccine is administered through intra-nasal route4. The efficacy of Abdala vaccine after three doses is 92.8%. These vaccines are world’s first conjugated vaccines and have been shown to be effective against the delta strain.  

The protein sub-unit-based vaccines exhibit a great promise for the development of future vaccines against highly mutated strains of COVID-19, such as Omicron, that has been reported a few days back from South Africa. Omicron has 15 mutations in the RBD domain of the spike virus, 2 of which are common to Delta strain. Based on the mutations present in the RBD of Omicron variant, recombinant protein can be produced accordingly in the suitable host and a new vaccine booster shot can be made ready in a few weeks for emergency authorization and use. 

Companies such as Pfizer5, who developed the mRNA vaccine are contemplating starting a trial in which the third (booster) shot of its mRNA vaccine will be co-administered with its 20-valent pneumococcal vaccine candidate (20vPnC), in order to boost the antibody response against COVID-19. 

The technology used by Cuba to develop protein-based vaccines against COVID-19 can lead to development of vaccines against new mutated strains of SARS-CoV-2 virus in a relatively easier manner.  



  1. GAVI 2021. What are protein subunit vaccines and how could they be used against COVID-19? Available at subunit-vaccines-and-how-could-they-be-used-against-covid-19 
  1. Reardon S., 2021. Cuba’s bet on home-grown COVID vaccines is paying off. Nature. News. Published 22 November 2021. DOI: 
  1. Toledo-Romani M., 2021. Efficacy and safety of SOBERANA 02, a COVID-19 conjugate vaccine in heterologous three-dose combination. Preprint medRxiv. Published 06 November 2021. DOI: 
  1. Yaffe H (31 March 2021). “Cuba’s five COVID-19 vaccines: the full story on Soberana 01/02/Plus, Abdala, and Mambisa”. LSE Latin America and Caribbean blog. Retrieved 31 March 2021. 
  1. Pfizer 2021. News – Pfizer initiates study exploring coadministration of its 20-valent pneumococcal conjugate vaccine candidate along with a third dose of the pfizer-biontech covid-19 vaccine in older adults. Posted 24 May 2021. Available at 


Rajeev Soni
Rajeev Soni
Dr. Rajeev Soni (ORCID ID : 0000-0001-7126-5864) has a Ph.D. in Biotechnology from the University of Cambridge, UK and has 25 years of experience working across the globe in various institutes and multinationals such as The Scripps Research Institute, Novartis, Novozymes, Ranbaxy, Biocon, Biomerieux and as a principal investigator with US Naval Research Lab in drug discovery, molecular diagnostics, protein expression, biologic manufacturing and business development.

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