BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

Abstract

The number of mutations in the omicron (B1.1.529) BA.1 variant of concern (VOC) led to an unprecedented evasion of vaccine induced immunity. However, despite the remarkable rise in global infections, severe disease and death did not increase proportionally, linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of a new sublineage, BA.2, that is more transmissible compared to BA.1, despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine induced responses that may be key to protection against infection and disease. Here we comprehensively profiled the BNT162b2 vaccine induced response to several VOCs including the omicron BA.1 and BA.2, after the primary vaccine series, 8 months following vaccination, and after a boost. While vaccine induced immune responses were compromised against both Omicron sublineages, vaccine induced antibody isotype titers, FcγR3a- and FcγR3b-receptor binding levels, and non-neutralizing opsonophagocytic functions were significantly attenuated to the omicron BA.2 Spike compared to the BA.1 lineage. Conversely, FcγR2a and FcγR2b binding was elevated to BA.2 potentially contributing to persistent protection against severity of disease. These data point to an attenuation of particular non-neutralizing antibody properties that may be key to protection against transmission, but the maintenance of others that may continue to confer protection against disease.

Exploring the Role of Serology Testing to Strengthen Vaccination Initiatives and Policies for COVID-19 in Asia Pacific Countries and Territories: A Discussion Paper

“…Evidence on neutralization data found a 20-fold reduction in neutralization associated with the Omicron variant [94] and lower neutralizing antibody titers to BA.1 and BA.2 when compared with wild-type SARS-CoV-2 [76,95]. Studies indicate similar humoral responses among BA.1 and BA.2 [76,95,96]. This evidence complements the epidemiological observation of higher rates of reinfection reported for Omicron compared with other virus variants [70].…”

Development of a panel of three multiplex allele-specific qRT-PCR assays for quick differentiation of recombinant variants and Omicron subvariants of SARS-CoV-2

“…The BA.2 subvariant is becoming the predominant strain of SARS-CoV-2 by replacing the BA.1 subvariant with a higher transmissibility ( Chen and Wei, 2022 ). It is reported that BA.2 could potentially evade natural and vaccine-induced immunity, rather than BA.1 ( Bartsch et al., 2022 ). The discrepancies in transmissibility and pathogenicity between the BA.1 and BA.2 subvariants make it necessary to conduct differential diagnosis of the Omicron subvariants in COVID-19 patients ( Hamill et al., 2021 ).…”