Key result
BNT162b2-induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 variants diminished with age, with limited polyfunctional breadth and magnitude observed in individuals aged 65 years and older.
Why the study?
Vaccine induced neutralizing and non-neutralizing antibody functions and their synergy in promoting protection against SARS-CoV-2, especially in older adults, are not fully understood.
Does age affect the neutralizing and non-neutralizing antibody functions induced by the BNT162b2 mRNA vaccine in uninfected healthcare workers?
Observational (n=51)
Does age affect the neutralizing and non-neutralizing antibody functions induced by the BNT162b2 mRNA vaccine in uninfected healthcare workers?
Answers are grounded in this paper and cite their sources.
Vaccine-induced neutralizing and non-neutralizing antibody functions diminish with age, highlighting the need to study Fc functions to understand vaccine efficacy in vulnerable populations like the elderly.
Each novel SARS-CoV-2 variant renews concerns about decreased vaccine efficacy caused by evasion of vaccine induced neutralizing antibodies. However, accumulating epidemiological data show that while vaccine prevention of infection varies, protection from severe disease and death remains high. Thus, immune responses beyond neutralization could contribute to vaccine efficacy. Polyclonal antibodies function through their Fab domains that neutralize virus directly, and Fc domains that induce non-neutralizing host responses via engagement of Fc receptors on immune cells. To understand how vaccine induced neutralizing and non-neutralizing activities synergize to promote protection, we leverage sera from 51 SARS-CoV-2 uninfected health-care workers after two doses of the BNT162b2 mRNA vaccine. We show that BNT162b2 elicits antibodies that neutralize clinical isolates of wildtype and five variants of SARS-CoV-2, including Omicron BA.2, and, critically, induce Fc effector functions. FcγRIIIa/CD16 activity is linked to neutralizing activity and associated with post-translational afucosylation and sialylation of vaccine specific antibodies. Further, neutralizing and non-neutralizing functions diminish with age, with limited polyfunctional breadth, magnitude and coordination observed in those ≥65 years old compared to <65. 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.
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Bates et al. (2022) conducted an observational in SARS-CoV-2 (n=51). BNT162b2 mRNA vaccine was evaluated on Neutralizing and non-neutralizing antibody functions against SARS-CoV-2 wildtype and variants. BNT162b2-induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 variants diminished with age, with limited polyfunctional breadth and magnitude observed in individuals aged 65 years and older.
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