BNT162b2 and CZ02 neutralizing antibody titres lower against Omicron vs earlier variants

A study by the University of Hong Kong (HKU) has found that immune sera from mRNA-based BNT162b2 and inactivated CZ02 vaccine recipients have substantially reduced neutralizing antibody titres against the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

“The novel SARS-CoV-2 Omicron variant first identified in late November 2021 has >50 amino acid mutations, deletions or insertions compared with the ancestral virus strain first detected in December 2019. Because of the large number of mutations, especially at the spike protein receptor binding domain [RBD], there is a concern that the Omicron variant can escape antibody neutralization induced by the currently available coronavirus disease 2019 [COVID-19] vaccines,” wrote the researchers. “In this study, we determined the neutralization susceptibility of two local Omicron variant isolates to antibodies from COVID-19 vaccine recipients and compared it with the ancestral SARS-CoV-2 lineage A virus, the Beta variant, and the Delta variant.” [Clin Infect Dis 2021;doi:10.1093/cid/ciab1041]

Omicron variant was isolated from the combined nasopharyngeal-throat swabs of two COVID-19 patients in Hong Kong and introduced to serum specimens from a total of 50 adult vaccine recipients, of whom 25 had received BNT162b2 and 25 had received CZ02 (median age, 48 years). There was no statistically significant difference in age, sex, or comorbidities between recipients of the two different vaccines. All individuals had received two doses of each vaccine, and the serum specimens were collected 56 days after the first vaccination.

“Among BNT162b2 recipients, all serum specimens had a microneutralization titre of ≥10 against the ancestral virus, Beta variant and Delta variant. However, only 20 percent and 24 percent of serum specimens had an microneutralization titre of ≥10 against the two Omicron variant isolates, respectively,” reported the researchers.

The geometric mean microneutralization titers (GMT) against the two Omicron isolates were 39.9- and 35.7-fold lower than those of the ancestral lineage A virus, respectively (p<0.0001). The GMT against both Omicron variant isolates were also significantly lower than those against the Beta variant (p=0.0057 and p=0.0175, respectively) or the Delta variant (p<0.0001 for both).

Among CZ02 recipients, 100 percent and 68 percent of serum specimens had an microneutralization titre of ≥10 against the ancestral virus and Delta variant, respectively, but none of the serum specimens had a microneutralization titre of ≥10 against the Omicron variant isolates or the Beta variant.

“Our results corroborate those of recent preprint articles showing that the Omicron variant can escape from neutralizing monoclonal antibodies,” commented the researchers. [https://www.ahri.org/wpcontent/uploads/2021/12/MEDRXIV-2021-267417v1-Sigal.pdf; bioRxiv 2021;doi:10.1101/2021.12.07.470392] “However, our study adds two unique insights. Firstly, we tested sera from CZ02 recipients, which is especially important as CZ02 is widely used globally. Secondly, we tested an Omicron isolate with R346K mutation, which is of particular concern, given its location on the spike protein RBD.”

“The reduced susceptibility of the Omicron variant to vaccine-induced neutralizing antibodies, together with its rapid spread, suggests a need for new vaccines,” wrote the researchers. “However, preliminary data indicate that booster doses of BNT162b2 can enhance neutralizing antibody response against the Omicron variant. Therefore, booster doses should be recommended before newer-generation vaccines become available.”