Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2

Abstract

SummaryThe ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. In this study, we investigate public servants who had been vaccinated with two dose (82.7%) or three dose (14%) of either CoronaVac (CorV) or BNT162b2 (BNT). During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2×BNT 49.2% vs 3×BNT 16.6%, p<0.0001; 2×CorV 48.6% vs 3×CoV 20.6%, p=0.003). The third heterologous vaccination showed the lowest incidence (2×CorV+1×BNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.

Effectiveness and durability of BNT162b2 vaccine against hospital and emergency department admissions due to SARS-CoV-2 omicron sub-lineages BA.1 and BA.2 in a large health system in the USA: a test-negative, case-control study

“…Our findings are consistent with those of a 2022 study evaluating breakthrough BA.2 infections, in which people receiving three doses of BNT162b2 had a lower incidence of breakthrough SARS-CoV-2 infections (16·6%) than did people receiving only two doses (49·2%). 34 Although a previous study 34 showed that neutralising antibody titres were lower for BA.2 than for BA.1, it also showed that three doses of BNT162b2 enhanced neutralising activity against omicron and better activated spike protein-specific memory B cells compared with only two doses. 34 Other reports have also shown similar findings for the effectiveness of mRNA vaccines against severe BA.2-related outcomes, whereby two doses offer only partial protection that is meaningfully bolstered by a booster dose.…”

“… 34 Although a previous study 34 showed that neutralising antibody titres were lower for BA.2 than for BA.1, it also showed that three doses of BNT162b2 enhanced neutralising activity against omicron and better activated spike protein-specific memory B cells compared with only two doses. 34 Other reports have also shown similar findings for the effectiveness of mRNA vaccines against severe BA.2-related outcomes, whereby two doses offer only partial protection that is meaningfully bolstered by a booster dose. 22 , 23 , 24 A US study 35 of immunocompetent adults showed lower mRNA vaccine effectiveness against moderate and severe COVID-19-associated illness for BA.2 compared with BA.1.…”