The RBD-cVLP 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-cVLP adjuvanted 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.
The vaccine ABNCoV2 identified and advanced in the Prevent-nCoV project is subject to further clinical development by Bavarian Nordic A/S. In the Phase 2 clinical trial of ABNCoV2, without adjuvant, it was found that subjects, previously vaccinated with approved and marketed mRNA or adenoviral vaccines, acquired a significant boost to the neutralizing antibodies against the Omicron variant in the majority of subjects with a fold increase in the same range as against original Wuhan SARS-CoV2 variant. While the neutralizing antibody titers against Omicron were the lowest when compared to all other variants previously reported (Wuhan, Alpha, Beta and Delta) they were boosted to levels associated with a high level of protection across both dose groups, 50μg and 100μg. In August 2021 it was announced that a funding agreement with the Danish Ministry of Health to further advance the development of ABNCoV2 had been entered. The agreement is valued at up to DKK 800 million and aims to support the completion of the development towards regulatory approval of ABNCoV2 as a booster vaccine, which could help strengthen the reliability and security of supply of COVID-19 vaccines and address the need for revaccination globally. The Phase III trial of ABNCoV2 was initiated in September 2022, with expected outcome in late 2022 potentially leading to regulatory approval of the vaccine in 2023.
The potential increased longevity of the antibody response, as in other capsid-based virus like vaccines, such as human papilloma virus vaccines, could reduce the need for frequent booster vaccinations. The vaccine may in later clinical development be combined with adjuvant to achieve even higher levels of protection and duration. In addition, ongoing pre-clinical investigations of mucosal administration to increase efficacy and reduce transmission, as well as administration of delta and omicron specific vaccines will demonstrate the versatility of the vaccine technology employed in the Prevent nCoV project.
We expect that after upscaling it will be possible to cost-efficiently produce in the order of billions of dosages a year. The short-term storage of the vaccine is compatible with ambient temperatures and the vaccine appears amenable to freeze dry storage. The preclinical, Phase I and Phase II immunological results look at least as good as the reported mRNA vaccines yielding 90-95% efficacy in Phase III trials. Thus, the RBD-cVLP vaccine is one of the most promising 2nd generation candidates for preventing COVID-19 disease and SARS-CoV-2 transmission. Moreover, the cVLP vaccine technology has now been added to the pandemic preparedness toolbox and will also be employed against endemic infectious diseases such as malaria, hepatitis and influenza.
