Periodic Reporting for period 1 - OPENCORONA (Rapid therapy development through Open nCoronavirus Vaccine Platform)
Reporting period: 2020-04-01 to 2021-03-31
The overall objectives of the project is to design universal SARS-CoV vaccine DNA candidates, evaluate immunogenicity in animal models and to select a candidate for clinical development to be evaluated in a phase 1 clinical trial. During the first year of the project a total of 24 different vaccine candidates has been designed by KI, produced and evaluated both in vitro and in vivo. Studies performed by KI, FoHM, JLU, IGEA and Adlego identified already in October 2020 a potential vaccine candidate that induced strong antibody, T cell responses as determined in mice, rabbits and ferrets. The studies leading up to the vaccine showed that although T cells alone can help to control the SARS-CoV-2 replication, the simultaneous presence of neutralizing antibodies (NAbs) are vital for an optimal protection. The gene consists of a highly modified version of the receptor binding domain (RBD) of Spike, the Nucleoprotein (N) and the Membrane (M) protein. The selected plasmid (OC2.3) was produced by Cobra (HQ DNA) for toxicological evaluation. In parallel with this work mutant strains of SARS-CoV-2 started to appear and we realized that this might impact on the spread of the virus and efficacy of the vaccines. The project therefore decided to adapt the vaccine to the most prominent mutations. This revealed a clear benefit with our vaccine design which is that we can include unique repeats of the RBD sequence and thereby include multiple mutant RBD sequences in the same vaccine construct. This updated vaccine construct (OC2.4) has now been evaluated in vivo and to induce very high levels of neutralizing antibodies against both Wuhan, B.1.1.7 and the B.1.351 strains. The final construct has now been forwarded to HQ and GM production by Cobra biologics. Importantly, the GMP production for the phase I clinical trial will also be sufficient for a coming phase 2 clinical trial of up to more than 500 subjects. Thus, the whole project is prepared for a continued clinical development of the project.
The work has resulted in one publication and several manuscripts under preparation. The project has focused on the laboratory work which is why only few scientifc publications has emanated from the project. The project has resulted in several patent applications that cover both the vaccine genes and the E-gun. The project has been highly exposed in media and many partners have been frequent guests in all types of national and international media such as TV, radio, Podcasts, webcasts, newspapers, and other media. Thus, the dissemination has been extremely effective.