Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination

Abstract

The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT₅₀) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT₅₀ titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.

Extended data Fig 1.. 90% plaque reduction neutralization test (PRNT90) antibody titres to wild-type virus and Omicron BA.1 variant.

PRNT90 antibody titres to Wild-type and Omicron Variant A. Individuals with 2 or 3 doses of BNT162b2 or CoronaVac vaccines, as indicated. B. SARS-CoV-2 convalescent individuals with or without BNT162b2 or CoronaVac vaccines (one dose). See table for numbers of individuals in each group. Mann-Whitney test (two tailed) was used for significance testing. P values are denoted. Dotted line indicates the threshold of protection and the shading indicates 95% confidence intervals (see text).

Extended data Fig2.. 50% plaque reduction neutralization test (PRNT50) antibody titres to wild-type virus, Omicron BA.1 variant and Delta variant in paired sera in six vaccinated individuals with breakthrough Omicron infections.

50% plaque reduction neutralization test (PRNT50) antibody titres wild type virus, Omicron variant and Delta variant in paired sera in six vaccinated individuals with breakthrough Omicron infections. The vaccine used in each individual is provided in the panel heading and clinical data provided in extended data table 2. Dotted line indicates PRNT50 threshold of protection and shading indicates 95% confidence intervals (see text).

Figure 1:. 50% plaque reduction neutralization test (PRNT₅₀) antibody titres to wild-type (WT) virus and Omicron BA.1 variant.

A. Individuals with 2 or 3 doses of BNT162b2 or CoronVac vaccines, as indicated. B. SARS-CoV-2 convalescent individuals with or without BNT162b2 or CoronaVac vaccine (one dose). C. PRNT₅₀ titres to Omicron in the different groups with geometric mean +/− SD are denoted. See Table for numbers of individuals in each group. Mann-Whitney test (two tailed) was used for significance testing. P values for each comparison are denoted. Dotted line indicates PRNT₅₀ threshold of protection and shading indicates 95% confidence intervals (see text).