Targeted vaccination against current and future corona viruses
The outbreak of the corona virus disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the imminent development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is becoming clear that SARS-CoV-2 succeeds in evading immunity, resulting in long recovery times and associated deaths.
The applicant research group has developed technology, called immuno-Boost (iBoost), for the effective vaccination against non- or low-immunogenic proteins in cancer, through recombinant designer proteins. This technology has been licensed to CimCure B.V, a partner in the consortium for this project. iBoost is perfectly suited for targeted vaccination against preferred domains in the spike protein S of SARS-CoV-2, thereby overcoming immune evasion. As SARS-CoV-2 enters cells through binding of S, via its Receptor Binding Domain (RBD), to the cellular receptor angiotensin converting enzyme-2 (ACE-2), it is likely that antibody responses against RBD will prevent infection, as was demonstrated for other coronaviruses.
The iBoost technology will be used to make vaccines against RBD of SARS-CoV-2. This will be done following a number of different strategies. Strategy 1 will fast track a full RBD protein vaccine, and is planned to have a product for testing in the clinic after 6 months. Strategy 2 is based on targeting conserved sequences of RBD of SARS-COV-2 and previous coronaviruses (SARS-CoV and MERS-CoV). An engineered construct with these sequences will be produced. Strategy 3 is based on the best exposed domains in RBD. It was found that these sequences are among the most conserved regions in RBD, a finding that suggests these sequences of key importance for virus entry into cells.
Vaccines from all three approaches will be tested in a validated hamster model that is available to the consortium. Generated antibodies will be tested in in vitro virus neutralisation assays, as well as in vivo for protection against SARS-CoV-2-induced adverse effects/infection. It is expected that at least one vaccine will enter clinical studies after 6 months (vaccine #1) or at the end of the project (vaccines #2 and #3).
