Oral SARS-CoV-2 vaccine uses bacteria to induce antibodies

First stage of the study reveals promising data on immune system activation
29 jun 2021


Bacteria that have SARS-CoV-2 virus proteins on their surface are the basis of a potential oral vaccine that is being studied by researchers from the IGC and ITQB NOVA, in a joint effort to find more tools to stop the current pandemic. The second phase of the study will assess the quality of the immune system’s response and the strength of protection against infection conferred after taking this vaccine.

The main tools that are available to fight this pandemic include vaccination for immunization and individual protection measures. Although there are already several vaccines on the market, production limitations and universal availability are still a challenge. The idea of ​​developing an oral vaccine using bacteria is not new and can be quickly scalable, with reduced costs, reaching more people in countries where cooling chains and vaccine application capacity may be limited. Instituto Gulbenkian de Ciência and Instituto de Tecnologia Química e Biológica António Xavier from Universidade NOVA de Lisboa have been studying for several years the different bacteria with which we live and the potential of some of them to induce the production of antibodies that protect against diseases. The discovery that a modified bacterium can lead its host to develop antibodies that protect it against malaria, the ability to trigger an immune response from the gut, and the study of the ability of bacterial spores to act as vehicles for transporting proteins of interest were previous studies that led to the study design of a new vaccine.

Isabel Gordo, principal investigator at the IGC, has been studying bacteria and their interaction with the organism for over 10 years. Bringing together the accumulated knowledge in recent years of the IGC’s multidisciplinary team was the critical piece to move forward. “We intend to express a part of the Spike protein in a bacterium, administer it as a probiotic and stimulate an immune response capable of facing the infection caused by SARS-CoV-2”. At ITQB NOVA, researchers Adriano Henriques and Mónica Serrano have also been studying bacterial spores for decades, cellular structures that are metabolically dormant and capable of resisting extreme environmental conditions: “spores formed by certain bacteria are able to survive when exposed to extreme physical and chemical conditions. We had to ensure this so that the bacteria administered orally can reach the intestines intact, where it will act and stimulate the immune system”, explains the researcher. The spore resistance properties are also an advantage for their storage and transport, which do not require a cold chain, he adds.

Researchers from both institutes produced a recombinant bacterium that produces spores with a part of the Spike protein of the SARS-CoV-2 virus on its surface. The part of the Spike protein in question is responsible for binding the virus to the host and also the one that can trigger a protective immune response. “The results of the first trials are very promising and take us to the next stage, in which we will assess the necessary ammount of spores to be administered to the host, to ensure an adequate response, and test it in an animal model exposed to the virus to measure the ability to respond to the disease”, explains Isabel Gordo. The great advantage of this solution is that “large-scale production is extremely easy, costs are reduced and the structure of the introduced Spike is easily modified, an advantage when we have virus mutations arising and it is necessary to adjust vaccines” adds Isabel.

In the last stage of the project, it is necessary to test the ability of this vaccine in a protected laboratory environment, since it is carried out with the active SARS-CoV-2 virus. The study will take place in a level 3 Biosafety laboratory, which the IGC has just built, as a result of a strategic reinforcement of the facilities to extend the research to other studies with active viruses and bacteria. The development of this project is based on a strategy focused on the mission and values ​​of the Calouste Gulbenkian Foundation with a view to improving the quality of life of the population and as a contribution to equal opportunities in society, and ITQB NOVA, to promote science and technology for the benefit of human health and the environment.

The next critical steps are based on the multidisciplinary team of several IGC laboratories whose research in immunology and genetics will be essential for the project’s success: Luís Moita, Moises Mallo, Jocelyne Demengeot, Maria João Amorim, Miguel Soares and Jonathan Howard laboratories.

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