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Rapid therapy development through Open nCoronavirus Vaccine Platform

Periodic Reporting for period 1 - OPENCORONA (Rapid therapy development through Open nCoronavirus Vaccine Platform)

Reporting period: 2020-04-01 to 2021-03-31

The OPENCORONA project aims at developing a universal SARS-CoV vaccine that is able to induce immune responses that cross react with viruses still present in animals. Although there has been a tremendous success in vaccine development globally to curb the current COVID-19 pandemic, there is almost a complete lack of vaccines that induce broadly reactive neutralizing antibodies and T cells that can help protect against future SARS-CoV outbreaks. This is the target for the OPENCORONA project, a universal SARS-CoV vaccine. Thus, the OPENCORONA project fills a gap in the COVID-19 vaccine space which is, for very good reasons, currently is focused on COVID-19. Our vaccine perfectly complements existing vaccines by inducing broadly cross-reactive neutralizing antibodies (NAbs) and T cells. These responses should be able to curb new SARS-CoV infections by complementing the responses induced by the current vaccines. Our approach is to induce broadly cross-reactive NAbs, combined with T cell responses that can prevent hospitalization and death from future SARS-CoV outbreaks. This is supported by the observation that T cells from patients infected by SARS-CoV in 2003 retained their reactivity until 2020. Thus, maintained immunity for 17 years post a SARS-CoV infection that cross-reacted with proteins from SARS-CoV-2. This suggested that those experiencing a SARS-CoV infection in 2003, albeit very few, most likely are immune to SARS-CoV-2. This strongly support the concept of a universal SARS-CoV vaccine to be used as a booster vaccine to broaden the protective immunity to also cover future SARS-CoVs most likely emanating from animals. This type of complementary vaccine has important implications for the society as a whole.

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 project has identified a vaccine candidate that induce antibodies that neutralize different SARS-CoV-2 strains, and T cells that recognize T cells that even recognize proteins from Bat and Pangolin viruses. The original vaccine candidate induced T cells that alone can reduce SARS-CoV-2 replication in ferrets and eliminate virus in the lungs. Moreover, the same vaccine induces NAb and T cell responses in NHPs that mediate clearance of SARS-CoV-2 in the lungs. The final version of the vaccine contain RBD loops from the Wuhan, B.1.1.7 and B.1.351 strains, and the M and N proteins from the Wuhan strain. This version effectively induce NAbs and neutralize both the Wuhan and B.1.351 strains. This vaccine is currently produced according to GMP in quantities sufficient for both phase 1 and 2 clinical trials containing more than 500 subjects. The DNA vaccine is delivered by the EGun, a new CE marked single step injection and in vivo electroporation device developed within the OPENCORONA 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.
The OPENCORONA vaccin is clearly beyond the current state of the art. The OPENCORONA developed universal SARS-CoV vaccine is intended to be used as a booster vaccine to broaden the protective immunity to also cover future SARS-CoVs most likely emanating from animals. Thus, existing vaccines that induce NAbs and T cells to the SARS-CoV-2 Spike protein needs to be complemented by future safe vaccines that induce NAbs and T cells to diverse and possible future SARS-CoVs. This type of complementary vaccine has important implications for the society as a whole and is essential for pandemic preparedness.
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