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Differential durability of humoral and T cell immunity after two and three BNT162b2 vaccinations in adults aged >80 years

A third mRNA-based "booster" vaccination is the favored strategy to maintain protection against SARS-CoV-2 infection. Yet, significant waning of specific immunity within six months after 2nd vaccination, along with higher incidence of breakthrough infections associated with the time elapsed since 2nd vaccination raises concerns regarding the durability of immunity also after 3rd vaccination. We address the currently debated consequence of a third vaccination against SARS-CoV-2 for generating durable immunity especially in older adults. Specifically, we assessed virus-specific serum antibody and single cell blood T cell responses after vaccination with the mRNA vaccine BNT162b2 in more than 50 individuals older than 80 years. All old adults demonstrate a strong humoral response to 3rd vaccination which is higher and wanes slower than the response to 2nd vaccination, indicative of enhanced humoral immunity. In contrast, their respective T cell response reaches only the level obtained after 2nd vaccination, with similar waning over time and no enhancement of IFN{gamma} production per cell. Because BNT162b2-mediated protection from the Omicron variant relies more on T cells than antibodies, our findings raise concern on the durability of protection from the Omicron variant by BNT162b2 in a population at risk.