T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals

Bilich, Tatjana; Nelde, Annika; Heitmann, Jonas S.; Maringer, Yacine; Roerden, Malte; Bauer, Jens; Rieth, Jonas; Wacker, Marcel; Peter, Andreas; Hörber, Sebastian; Rachfalski, David; Märklin, Melanie; Stevanović, Stefan; Rammensee, Hans‐Georg; Salih, Helmut R.; Walz, Juliane S.

doi:10.1126/scitranslmed.abf7517

Cited by 144 publications

(168 citation statements)

References 85 publications

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“…In line with our results, several recent studies also reported that the T-cell responses to SARS-CoV-2 were maintained in patients up to 6 months after the onset of COVID-19 symptoms. [22][23][24] However, another group found that the frequencies of spike-specific CD4 + T cells declined in the first 4 months POS. 25 Indeed, in our study, either CD4 + or CD8 + T-cell response waned in some patients.…”

Section: Discussionmentioning

confidence: 99%

Decline in neutralising antibody responses, but sustained T‐cell immunity, in COVID‐19 patients at 7 months post‐infection

et al. 2021

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Objectives This study aimed to explore the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐specific humoral responses and T‐cell responses in patients who have recovered from coronavirus disease 2019 (COVID‐19) to understand the natural protective immune responses and to facilitate the development of vaccines. Methods We conducted a combined assessment of the changes in neutralising antibody levels and SARS‐CoV‐2‐specific T‐cell responses over time in 27 patients up to 7 months after infection. Results The neutralising antibody remained detectable in 96.3% of the patients at their second visit at about 7 months post‐onset of symptoms. However, their humoral responses, including titres of the spike receptor‐binding domain IgG and neutralising antibody, decreased significantly compared with those at first clinic visit. By contrast, the proportions of spike‐specific CD4+ T cells, but not CD8+ T cells, in COVID‐19 patients after recovery were persistently higher than those in healthy controls. No significant change was observed in the proportion of spike‐specific CD4+ T cells in patients who had recovered from COVID‐19 within 7 months. Conclusion The SARS‐CoV‐2‐specific T‐cell immune responses persisted, while the neutralising antibodies decayed. Further studies are needed to extend the longevity of neutralising antibodies and to evaluate whether these T cells are sufficient to protect patients from reinfection.

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Section: Discussionmentioning

confidence: 99%

Decline in neutralising antibody responses, but sustained T‐cell immunity, in COVID‐19 patients at 7 months post‐infection

et al. 2021

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“…In order to control future outbreaks and identify at-risk individuals, the exact constituents of effective COVID-19 immunity at a population level must be understood. When used alongside measurements of virus-specific antibodies, T cell response readouts represent a powerful, additional measure of potential immunity from COVID-19, with a higher degree of confidence than either measurement on their own, in particular given the concern on the longevity of measurable antibody responses (21)(22)(23). In addition, the FDA's decision to issue emergency use authorisation for a SARS-CoV-2 T cell test highlights the growing acceptance and usefulness of T cell testing for the clinical management of certain patient groups (24).…”

Section: Discussionmentioning

confidence: 99%

Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers

Scurr

Zelek

Lippiatt³

et al. 2021

Preprint

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Accurate assessment of SARS-CoV-2 immunity in the population is critical to evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T cell responses are a critical feature of the immune response that will likely form a key correlate of protection against COVID-19. Here, we developed and optimised a high-throughput whole blood-based assay to determine the T cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 156 healthy donors and 67 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were harvested and analysed for Th1-type effector cytokines (IFN-γ and IL-2). Amongst healthy donors, highly significant differential IFN-γ+/IL-2+ SARS-CoV-2-specific T cell responses were seen amongst vaccinated or previously infected COVID-19-positive individuals in comparison to unknown/naïve individuals (P < 0.0001). IL-2 production from T cells in response to SARS-CoV-2 derived antigens was a highly predictive diagnostic assay (P < 0.0001; 96.0% sensitivity, 93.9% specificity); measurement of IFN-γ+ SARS-CoV-2 specific T cell responses was equally effective at identifying asymptomatic (antibody and T cell positive) participants. A single dose of COVID-19 vaccine induced IFN-γ and/or IL-2 SARS-CoV-2-specific T cell responses in 28/29 (96.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P = 0.0003). Overall, this cost-effective standardisable test ensures accurate and comparable assessments of SARS-CoV-2-specific T cell responses amenable to widespread population immunity testing.

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“…Recent studies on immunological responses against SARS-CoV-2 provided a detailed picture of immune signatures in COVID-19 patients (either with severe disease, mildly symptomatic or asymptomatic) as compared to convalescent individuals, people that have been in close contact with a COVID-19 patient, and unexposed healthy donors. Such studies consistently reported a major role of T cell responses in developing immunity against SARS-CoV-2 [ 53 , 55 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. Notably, T cell responses were shown to be polyfunctional (involving both CD4+ and CD8+ lymphocytes), stable, and lasting for at least six months after infection, even though anti-SARS-CoV-2 antibodies decline with time [ 63 , 65 , 69 ].…”

Section: Do Repeated Exposures To Low Sars-cov-2 Doses Induce T Cell Immunity? a Possible Explanation For Sars-cov-2-specific T Cell Respmentioning

confidence: 95%

“…Such studies consistently reported a major role of T cell responses in developing immunity against SARS-CoV-2 [ 53 , 55 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. Notably, T cell responses were shown to be polyfunctional (involving both CD4+ and CD8+ lymphocytes), stable, and lasting for at least six months after infection, even though anti-SARS-CoV-2 antibodies decline with time [ 63 , 65 , 69 ]. Moreover, SARS-CoV-2-specific T cells with a stem-like memory phenotype (CCR7+CD127+CD45RA−/+TCF1+) were identified in COVID-19 convalescent subjects, even in the absence of detectable circulating antibodies, highlighting the role of memory T cells in sustaining long-term immunity against SARS-CoV-2 [ 67 ].…”

Section: Do Repeated Exposures To Low Sars-cov-2 Doses Induce T Cell Immunity? a Possible Explanation For Sars-cov-2-specific T Cell Respmentioning

confidence: 95%

Repeated Exposure to Subinfectious Doses of SARS-CoV-2 May Promote T Cell Immunity and Protection against Severe COVID-19

Angelis

Francescangeli

Rossi

et al. 2021

Viruses

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Europe is experiencing a third wave of COVID-19 due to the spread of highly transmissible SARS-CoV-2 variants. A number of positive and negative factors constantly shape the rates of COVID-19 infections, hospitalization, and mortality. Among these factors, the rise in increasingly transmissible variants on one side and the effect of vaccinations on the other side create a picture deeply different from that of the first pandemic wave. Starting from the observation that in several European countries the number of COVID-19 infections in the second and third pandemic wave increased without a proportional rise in disease severity and mortality, we hypothesize the existence of an additional factor influencing SARS-CoV-2 dynamics. This factor consists of an immune defence against severe COVID-19, provided by SARS-CoV-2-specific T cells progressively developing upon natural exposure to low virus doses present in populated environments. As suggested by recent studies, low-dose viral particles entering the respiratory and intestinal tracts may be able to induce T cell memory in the absence of inflammation, potentially resulting in different degrees of immunization. In this scenario, non-pharmaceutical interventions would play a double role, one in the short term by reducing the detrimental spreading of SARS-CoV-2 particles, and one in the long term by allowing the development of a widespread (although heterogeneous and uncontrollable) form of immune protection.

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T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals

Cited by 144 publications

References 85 publications

Decline in neutralising antibody responses, but sustained T‐cell immunity, in COVID‐19 patients at 7 months post‐infection

Decline in neutralising antibody responses, but sustained T‐cell immunity, in COVID‐19 patients at 7 months post‐infection

Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers

Repeated Exposure to Subinfectious Doses of SARS-CoV-2 May Promote T Cell Immunity and Protection against Severe COVID-19

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