Neutralizing Activity Against SARS-CoV-2 Delta and Omicron Variants Following a Third BNT162b2 Booster Dose According to Three Homologous or Heterologous COVID-19 Vaccination Schedules

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND₅₀ against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND₅₀ against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND₅₀ against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.