Immunogenicity of a third dose of BNT162b2 to ancestral SARS-CoV-2Omicron variant in adults who received two doses of inactivated vaccine

Limited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants.We conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT.In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p 0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p 0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by 45 fold from Day 0 to Day 28 against the ancestral virus (p 0.001) and rose by 11 fold against the Omicron variant (p 0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants.A third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.