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 IFNγ 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.
The circulating nucleocapsid (NCP) antigen of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is detectable in coronavirus disease‐2019 (COVID‐19) patients. To better understand the biology of disease severity, we investigated NCP clearance kinetics in hospitalized COVID‐19 patients. Serum NCP was quantified using a commercial NCP‐specific enzyme‐linked immunoassay in hospitalized COVID‐19 patients (n = 63) during their hospital stay. Results were correlated to COVID‐19 disease severity, inflammation parameters, antibody response, and results of SARS‐CoV‐2 PCR from nasopharyngeal swabs. We demonstrate that NCP antigen levels in serum remained elevated in 21/45 (46.7%) samples from patients in intensive care units (ICU) after >8 days postdiagnosis. The proportion of ICU patients with detectable antigenemia declined only gradually from 84.6% to 25.0% over several weeks. This was in contrast to complete NCP clearance in all non‐ICU patients after 8 days, and also in contrast to mucosal clearance of the virus as measured by PCR. Antigen clearance was associated with higher IgG against S1 but not NCP. Clearance of NCP antigenemia is delayed in >40% of severely ill COVID‐19 patients. Thus, NCP antigenemia detected after 8 days post COVID‐19 diagnosis is a characteristic of patients requiring intensive care. Prospective trials should further investigate NCP antigen clearance kinetics as a mechanistic biomarker.
Herein, we compared SARS-CoV-2-specific antibody and T-cell responses to two doses of BNT162b2 mRNA in 51 vaccinees > 80 years old and 46 (20–53 years old) controls. The responses of the elderly were much lower and 10% non-responders were identified. Importantly, in four of them, a third vaccination raised the immune response to levels seen in responders after two vaccinations, thus implying that non-response is not fateful even in the elderly.
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