Introduction
beta variant infection, beta variant RBD, deaths, coronavirus disease 2019
CORONAVIRUS, SEVERE ACUTE RESPIRATORY SYNDROME, CORONAVIRUS DISEASE 2019, ADVERSE EVENTS
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has created an enormous global health crisis, with more than 767 million confirmed cases and more than 6.9 million deaths.Although effective COVID-19 vaccines have been rapidly developed and deployed, a succession of variants of concern (VOC) have emerged since mid 2020. The beta VOC was first detected in South Africa in late 2020In addition to the emergence of vaccine-resistant variants, many challenges remain, including: vaccine stability during storage and transport and access for developing countries, waning vaccine-induced immunity, and concerns about rare, yet serious, adverse events associated with existing Spike-based vaccines. Immunological imprinting also seems to be limiting the impact of new variant-targeting bivalent Spike vaccines,We have developed two vaccine candidates based on the SARS-CoV-2 beta variant RBD: an adjuvanted recombinant protein, and a nucleoside-modified mRNA delivered in lipid nanoparticles. The beta variant was selected because at the time we initiated production, this was the most immuno-evasive variant. This was fortuitous because, as mentioned above, beta variant infection and vaccines appear to drive superior cross reactivity compared to the ancestral strain.Our preclinical studies showed that the beta RBD protein vaccine as a third injection provided a stronger immune boost for generating RBD-targeting antibodies, including nAb, compared to a third ancestral or beta variant whole Spike vaccine boost.