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Prevention of SARS-CoV-2 infection through development and clinical testing of a novel Virus Like Particle (VLP) vaccine

Periodic Reporting for period 1 - Prevent-nCoV (Prevention of SARS-CoV-2 infection through development and clinical testing of a novel Virus Like Particle (VLP) vaccine)

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

The Prevent-nCoV consortium has during the last year generated pre-clinical proof of concept as well as cGMP manufacture, toxicological studies for capsid like delivery of SARS-CoV-2 antigens, as well as initiated a clinical trial. According to the original plan the consortium has suffered only a slight delay due to sourcing of resins and Covid-19 outbreaks and quarantine at the manufacturing sites. This enabled the rapid development of a SARS-CoV-2 vaccine, which is a global priority.

The Prevent-nCoV consortium’s objective is to develop and perform a proof-of-concept study for
• a highly effective (>80% protection)
• rapidly protective (within 2 weeks of vaccination)
• SARS-CoV-2 sub-unit vaccine (Spike antigen displayed on a capsid Virus-Like Particle)
• within 11 months initiate a Phase I/IIa clinical study
• to help protect medical workers and the public from the current Coronavirus outbreak
The lead antigen is the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The antigen is expressed using the proprietary S2 system of Expres2ion biotechnologies. The RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher ensuring unidirectional and high-density display of RBD. The AP205 is expressed at high yield in E coli. Both soluble recombinant RBD, and RBD displayed on CLPs bind the ACE2 receptor with nano-molar affinity.

The consortium early on identified the ideal partners for pre-clinical toxicological testing, Charles River/Scantox as well as for the cGMP production, AGC biologics. In July consortium member AdaptVac out licensed the vaccine to Bavarian Nordic to enable support during transfer and phase 1 and further clinical development.
The vaccine was named ABNCoV2 (AdaptVac/Bavarian Nordic Corona virus 2). The drug substance was shipped to filling site Q4 2020 under quarantine, and released mid Q1 2021. The completion of the submission of the clinical trial dossier resulted in approval of the COUGH1 (https://clinicaltrials.gov/ct2/show/NCT04839146) trial in early March 2021. The clinical Phase I/II trial is currently ongoing. The first group of 18 healthy volunteers have now been administered with two dosages of 6, 12 & 25 micro gram, with and without adjuvant. So far, the vaccine has been very well tolerated and first immunological investigations are ongoing. The study continues as planned with dosages up to 70 microgram in up to an additional 24 healthy volunteers in May and June 2021. The headline results of the complete study are expected to be released in July 2021.
The RBD-CLP vaccines induce more than 500-fold higher levels of neutralizing anti-RBD antibodies, than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice and non-human primates elicits virus neutralization antibody titers equal to those found in patients recovered from severe Covid-19 with the highest neutralizing capacity. Following booster vaccinations generated in mice and NHP, the virus neutralization titers exceed those measured after natural infection more than fifty times. Thus, the RBD-CLP vaccine is one of the most promising candidates for preventing COVID-19 disease and SARS-CoV-2 transmission. An additional experimental CLP vaccine based on the Spike S1 subunit, as well as intranasal administrations of the RBD-CLP are being investigated pre-clinically.

We expect that after upscaling it will be possible to produce in the order of billions of dosages a year at a low cost. The storage of the vaccine is compatible with ambient temperatures, the duration of which is being tested rigorously at the moment. The preclinical results are at least as good as the reported mRNA vaccines yielding 90-95% efficacy in phase 3 trials. The exceptional longevity of the antibody response of other capsid based vaccines, such as human papilloma capsid based vaccines, holds the potential of not only protection from but also reduction of transmission of SARS-CoV-2.
Corona virus