Delayed Antibody and T-Cell Response to BNT162b2 Vaccination in the Elderly, Germany

Schwarz, Tatjana; Tober‐Lau, Pinkus; Hillus, David; Helbig, Elisa T; Lippert, Lena J; Thibeault, Charlotte; Koch, Willi; Landgraf, Irmgard; Michel, Janine; Bergfeld, Léon; Niemeyer, Daniela; Mühlemann, Barbara; Conrad, C.; Dang-Heine, Chantip; Kasper, Stefanie; Münn, Friederike; Kappert, Kai; Nitsche, Andreas; Tauber, Rudolf; Schmidt, Sein; Kopankiewicz, Piotr; Bias, Harald; Seybold, Joachim; Kalle, Christof von; Jones, Terry C.; Suttorp, Norbert; Drosten, Christian; Sander, Leif Erik; Corman, Victor M.; Kurth, Florian

doi:10.3201/eid2708.211145

Cited by 74 publications

(67 citation statements)

References 12 publications

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“…However, despite the limited sample size and the short interval between second vaccination and infection, this outbreak raises questions about the effectiveness of the vaccination regimen in the elderly (3,8,(10)(11)(12). A delayed and overall reduced immune response to BNT162b2 vaccination has been described in elderly persons (13,14), which might explain the reported outbreak and infections in LTCF described elsewhere (4,5). This outbreak highlights that older adults have reduced protection <2 weeks after second BNT162b2 vaccination.…”

Section: Discussionmentioning

confidence: 96%

Outbreak of SARS-CoV-2 B.1.1.7 Lineage after Vaccination in Long-Term Care Facility, Germany, February–March 2021

Tober‐Lau¹,

Schwarz²,

Hillus³

et al. 2021

Emerg. Infect. Dis.

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O utbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in long-term care facilities (LTCF) are of great concern and have been reported to have high case-fatality rates (1). Consequently, national vaccination strategies prioritize residents of LTCFs (2).The coronavirus disease (COVID-19) mRNA vaccine BNT162b2 (Pfi zer-BioNTech, https://www.pfi zer.com) has demonstrated high effi cacy against COV-ID-19 (3). Protection has been observed >12 days after the fi rst vaccination, and reported vaccine effi cacy is 52% between the fi rst and second dose and 91% in the fi rst week after the second dose (3). Although breakthrough infections have been reported, vaccinated persons were at substantially lower risk for infection and symptomatic disease (4,5).The variant of concern (VOC) B.1.1.7 rapidly became the predominant lineage in Europe in 2021. Analyses estimated that B.1.1.7 has increased transmissibility and a <0.7 higher reproduction number (6). Neutralization activity of serum samples from BNT162b2-vaccinated persons has been shown to be slightly reduced against B.1.1.7 in cell culture ( 7), but observational data from Israel suggest BNT162b2 vaccination is effective against B.1.1.7 (8).We investigated a SARS-CoV-2 B.1.1.7 outbreak in a LTCF, which involved 20 BNT162b2-vaccinated residents and 4 unvaccinated residents. We report on clinical outcomes, viral kinetics, and control measures applied for outbreak containment. The study was approved by the ethics committee of Charité-Universitätsmedizin Berlin (EA2/066/20) and conducted in accordance with the Declaration of Helsinki and guidelines of Good Clinical Practice (https://www.ema. europa.eu/en/documents/scientifi c-guideline/ich-e-6-r2-guideline-good-clinical-practice-step-5_en.pdf). The StudyOn February 4, 2021, daily SARS-CoV-2 screening of employees yielded a positive antigen point-ofcare test (AgPOCT) result in 1 caregiver in a LTCF in Berlin, Germany. Among 24 residents of the unit under their responsibility, 20 (83%) residents had received the second dose of BNT162b2 on January

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Section: Discussionmentioning

confidence: 96%

Outbreak of SARS-CoV-2 B.1.1.7 Lineage after Vaccination in Long-Term Care Facility, Germany, February–March 2021

Tober‐Lau¹,

Schwarz²,

Hillus³

et al. 2021

Emerg. Infect. Dis.

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“…2,3 The emergence of variants of concern (VOC), particularly Delta (B.1.617.2), has raised concerns about waning protection, particularly in risk populations such as the elderly, who display reduced immune responses to BNT162b2 vaccination compared to younger adults. 4 In light of increasing infection rates caused by the Delta VOC, authorities in several countries, including in the United States, Israel, and Germany, are discussing or have recently begun offering a booster dose to vulnerable populations, such as all persons over 60 years of age. However, the durability of vaccine-induced immunity in the elderly is currently unknown.…”

Section: Main Textmentioning

confidence: 99%

“…However, the durability of vaccine-induced immunity in the elderly is currently unknown. Following up on a previous analysis, we describe interim results of a prospective cohort study comparing immune responses in a cohort of vaccinated elderly persons to those in healthcare workers (HCW) 4,5 , measured six months after first immunisation with BNT162b2. 1).…”

Section: Main Textmentioning

confidence: 99%

“…Study participants were recruited in the EICOV, COVIMMUNIZE, and COVIM studies, three prospective cohort studies conducted under the auspices of Charité -Universitätsmedizin Berlin, Germany, in accordance with the Declaration of Helsinki and Good Clinical Practice. 4,5 EICOV and COVIMMUNIZE studies were approved by the local ethics committee of Charité -Universitätsmedizin Berlin (EA4/244/20, EA4/245/20), and COVIM was approved by the Federal Institute for Vaccines and Biomedicines (Paul Ehrlich Institute) and by the ethics committee of the state of Berlin (EudraCT-2021-001512-28). Written informed consent was obtained by all participants, according to local and national regulations.…”

Section: Study Participantsmentioning

confidence: 99%

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Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers

Tober‐Lau

Schwarz

Vanshylla

et al. 2021

Preprint

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COVID-19 mRNA vaccine BNT162b2 is highly immunogenic and effective, but recent studies have indicated waning anti-SARS-CoV-2 immune responses over time. Increasing infection rates has led authorities in several countries to initiate booster campaigns for vulnerable populations, including the elderly. However, the durability of vaccine-induced immunity in the elderly is currently unknown. Here, we describe interim results of a prospective cohort study comparing immune responses in a cohort of vaccinated elderly persons to those in healthcare workers (HCW), measured six months after first immunisation with BNT162b2. Anti-SARS-CoV-2 S1-, full Spike- and RBD -IgG seropositivity rates and IgG levels at six months were significantly lower in the elderly compared to HCW. Serum neutralization of Delta VOC measured by pseudovirus neutralisation test was detectable in 43/71 (60.6%, 95%CI: 48.9-71.1) in the elderly cohort compared to 79/83 in the HCW cohort (95.2%, 95%CI: 88.3-98.1) at six months post vaccination. Consistent with the overall lower antibody levels, SARS-CoV-2-S1 T cell reactivity was reduced in the elderly compared to HCW (261.6 mIU/ml, IQR:141.5-828.6 vs 1198.0 mIU/ml, IQR: 593.9-2533.6, p<0.0001). Collectively, these findings suggest that the established two-dose vaccination regimen elicits less durable immune responses in the elderly compared to young adults. Given the recent surge in hospitalisations, even in countries with high vaccination rates such as Israel, the current data may support booster vaccinations of the elderly. Further studies to determine long-term effectiveness of COVID-19 vaccines in high-risk populations and the safety and effectiveness of additional boosters are needed.

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“…Vaccines against SARS-CoV-2 have proven high effectiveness among at-risk populations such as the elderly 1 , patients on maintenance hemodialysis 2 or individuals suffering from chronic inflammatory diseases under selected immunosuppressive regimens 3 . In contrast to the latter, kidney transplant recipients (KTR) receiving immunosuppressive medication exhibit strongly reduced humoral as well as impaired B and T cell responses after mRNA-based vaccination [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients

Schrezenmeier

Rincón‐Arévalo

Stefanski

et al. 2021

Preprint

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Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

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Delayed Antibody and T-Cell Response to BNT162b2 Vaccination in the Elderly, Germany

Cited by 74 publications

References 12 publications

Outbreak of SARS-CoV-2 B.1.1.7 Lineage after Vaccination in Long-Term Care Facility, Germany, February–March 2021

Outbreak of SARS-CoV-2 B.1.1.7 Lineage after Vaccination in Long-Term Care Facility, Germany, February–March 2021

Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers

B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients

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