Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults

Romero‐Olmedo, Addi J.; Schulz, Axel; Hochstätter, Svenja; Gupta, Dennis Das; Virta, Iiris; Hirseland, Heike; Staudenraus, Daniel; Camara, Bärbel; Münch, Carina; Hefter, Véronique; Sapre, Siddhesh; Krähling, Verena; Müller-Kräuter, Helena; Widera, Marek; Mei, Henrik E.; Keller, Christian; Lohoff, Michael

doi:10.1038/s41564-021-01046-z

Cited by 64 publications

(61 citation statements)

References 12 publications

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“…Concentrations of S1- and RBD-specific IgG also declined from the acute responses at week 5 and week 26, but clearly at a lower rate after 3 rd (week 40) compared to 2 nd (week 24) vaccination (Fig.1B,E, sFig.1A, sFig.2), yielding persistently enhanced IgG quantity and/or quality after the 3 rd vaccination. We conclude that a third vaccination against SARS-CoV-2 in older adults, while establishing immunity in primary non-responders 4 , induces a durably escalated humoral response in the bulk of vaccinees for at least three months, indicating longer lasting humoral immunity. However, BNT162b2-induced immune reactivity against the emerging Omicron variant is predominantly T cell-mediated 5,6 .…”

Section: Main Textmentioning

confidence: 81%

“…We compared the specific humoral and cellular response (Fig.1A-C) after 3 rd vs. 2 nd vaccination with BNT162b2 in a cohort of adults aged >80 years (sTable1,2 4 ) at risk for severe COVID-19 and immune senescence. Our data demonstrate the induction of marginally higher spike S1-specific blood IgG concentrations two weeks after 3 rd than after 2 nd vaccination (sFig.1A, Fig.1D).…”

Section: Main Textmentioning

confidence: 99%

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

Romero‐Olmedo

Schulz

Hochstätter

et al. 2022

Preprint

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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.

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Section: Main Textmentioning

confidence: 81%

Section: Main Textmentioning

confidence: 99%

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

Romero‐Olmedo

Schulz

Hochstätter

et al. 2022

Preprint

Self Cite

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show abstract

“…We conclude that a third dose of BNT162b2 in older adults, while establishing immunity in primary non-responders, 4 induces a durably escalated humoral response in the bulk of vaccinees for at least 3 months, indicating longer lasting humoral immunity. In a younger cohort, this boost also led to a strong increase of neutralising antibodies against the omicron (B.1.1.529) variant and protection from infection with the omicron variant.…”

mentioning

confidence: 80%

Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years

Romero‐Olmedo

Schulz

Hochstätter

et al. 2022

The Lancet Infectious Diseases

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“…It has been reported by us (2), (3) and others (4)(5)(6) that the cellular and humoral immune response wanes over time after infection and after vaccination. In the present study, we were primarily interested how anti SARS-CoV-2 antibodies and SARS-CoV-2 specific T-cell responses declined over time after two doses of mRNA vaccines, especially by age-group and comorbidity status.…”

Section: Introductionmentioning

confidence: 91%

Immune responses after twofold SARS-CoV-2 immunisation in elderly residents and Health Care Workers in nursing homes and homes with assisted living support - Proposal for a correlate of protection

Schiffner¹,

Eisemann²,

Baltus³

et al. 2022

Preprint

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In the present study, we were interested in the decline over time of anti SARS-CoV-2 antibodies and SARS-CoV-2 specific T-cell responses after two doses of mRNA vaccines in total and by age group and comorbidity. The second goal was to suggest an immunological correlate for protection on an individual basis and to describe the probability of protection over time after second vaccination. We analysed blood samples from 228 residents (median age 83.8 years) and from 273 Health Care Workers (HCW; median age 49.7 years) of five nursing homes and one home for the elderly with assisted living support. Participants had received two vaccinations. The blood samples were analysed for SARS-CoV-2 specific antibody and T-cell responses. We compared outcomes in the HCW and residents in the respective institutions. No breakthrough infections occurred during the study period. The initial immune responses in the younger participants were about 30 % higher than in the older ones. Over time, all parameters dropped continuously in all groups within the maximum observation period of 232 days. Comorbidities such as coronary heart disease or diabetes mellitus reduced the initial immune responses, regardless of age. In contrast to an almost linear decline in antibody levels, we observed that the interferon-gamma response remained at a constant level between about day 120 and 180, only to decline further thereafter. Based on our data, we propose on an individual level a correlate of protection: Persons who have a neutralizing capacity of 75 % (which would correspond to approx. 200 BAU/ml) and an interferon-gamma response above 200 mIU/ml should be considered to be protected resp. sufficiently immunized.

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Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults

Cited by 64 publications

References 12 publications

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

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

Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years

Immune responses after twofold SARS-CoV-2 immunisation in elderly residents and Health Care Workers in nursing homes and homes with assisted living support - Proposal for a correlate of protection

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