Each SARS-CoV-2 variant renews concerns about decreased vaccine neutralization weakening efficacy. However, while prevention of infection varies, protection from disease remains and implicates immunity beyond neutralization in vaccine efficacy. Polyclonal antibodies function through Fab domains that neutralize virus, and Fc domains that induce non-neutralizing responses via engagement of Fc receptors on immune cells. To understand how vaccines promote protection, we leverage sera from 51 SARS-CoV-2 uninfected individuals after two doses of the BNT162b2 mRNA vaccine. We show neutralizing activities against clinical isolates of wildtype and five SARS-CoV-2 variants, including Omicron BA.2, link to FcγRIIIa/CD16 non-neutralizing effector functions. This is associated with post-translational afucosylation and sialylation of vaccine specific antibodies. Further, polyfunctional neutralizing and non-neutralizing breadth, magnitude and coordination diminish with age. Thus, studying Fc functions in addition to Fab mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations such as the elderly against SARS-CoV-2 and novel variants.

Fuente: Cell Reports
Available online 5 October 2022, 111544