Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19

Bilich, Tatjana; Nelde, Annika; 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:10.21203/rs.3.rs-114499/v1

Cited by 4 publications

(7 citation statements)

References 35 publications

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“…Key characteristics of the control group populations are summarized in Table S6. Samples from human COVID-19 convalescent individuals (HCs) for analyses of T cell responses to specific and cross-reactive SARS-CoV-2 epitope compositions (EC) and samples for analyses of T cell responses after mRNA-based vaccines were previously described (9,14,18,41).…”

Section: Control Sample Cohortsmentioning

confidence: 99%

“…Although it is undisputed that neutralizing antibodies induced by COVID-19 vaccines provide the first line of antiviral defense (5,6), spike-specific antibody titers tend to wane quickly and show limited neutralizing activity against newly arising variants of concern (VOCs) (7). In contrast, T cells were shown to mediate long-term immunity that is largely conserved against VOCs after SARS-CoV-2 infection and vaccination (5,8,9). T cell immunity is of central importance for patients unable to mount humoral immune responses, comprising individuals with congenital B-cell deficiency, but also cancer patients with disease or treatment related B-cell depletion that are at high risk for a severe course of COVID-19 (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…CoVac-1 comprises six promiscuous HLA-DR-binding SARS-CoV-2-derived T cell epitopes from different viral proteins such as spike, membrane, nucleocapsid, envelope and open reading frame 8 (ORF8). These T cell epitopes were identified based on frequent and HLA-independent recognition by T cells in COVID-19 convalescents, their relevance for T cell immunity to combat COVID-19, and their ability to induce long-lasting immunity after infection (9,14,15). First results obtained in an open-label first-in-human phase I trial evaluating CoVac-1 in healthy adults for up to 3 months showed a favorable safety profile and induction of poly-specific T cell responses with intensities that exceeded those after natural SARS-CoV-2 infection and after vaccination with approved mRNA-based or adenoviral vectorbased vaccines (15).…”

Section: Introductionmentioning

confidence: 99%

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Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults

Tandler

Michael

Marconato

et al. 2023

Preprint

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Background: T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants. Method: We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human clinical trial and observed a favorable safety profile and induction of poly-specific T cell responses until month 3. Here, we report on long-term safety and efficacy data of CoVac-1 in healthy adults until month 12. Findings: CoVac-1 is well tolerated without long-term immune-related side effects and induces long-lasting anti-viral T cell responses in 100% of study participants. Potent expandability of CD4+ and CD8+ T cells targeting multiple different CoVac-1 T cell epitopes was observed 6 and 12 months after one single dose of CoVac-1. T cell responses were associated with the severity and the number of local adverse events at injection site. Beyond induction of T cell immunity, 89% of study participants developed CoVac-1-specific IgG antibody titers which associated with the intensity of the T cell response, indicating that CoVac-1-specific CD4+ T cells support the induction of B cell responses. Vaccination with approved COVID-19 vaccines boosted CoVac-1-specific T cell responses. Overall, a low SARS-CoV-2 infection rate was observed in the study population (8.3% of participants until month 12). Interpretation: Together, a single application of CoVac-1 elicits long-lived and broad SARS-CoV-2-specific T cell immunity, which further supports the current evaluation of our T cell activator in patients with congenital or acquired B cell defects (NCT04954469). Funding: This trial is funded by the Ministry of Science, Research and the Arts Baden-Wuerttemberg., Germany

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Section: Control Sample Cohortsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults

Tandler

Michael

Marconato

et al. 2023

Preprint

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“…Even COVID-19 infection demonstrated that T cell response is important to generate memory response and lower severity in infected patients (14,15,16,17). Other studies concluded that nucleocapsid protein has to be included in further vaccine strategy (18,19,20,21). This can be a promising strategy to curb circulating Delta (22), Omicron variants (23) and hybrids (24) simultaneously.…”

Section: Introductionmentioning

confidence: 99%

De novodesign of anti-variant COVID-19 Vaccine

Goswami

Shankar

Gore

2022

Preprint

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Recent studies have shown the efficacy of hybrid COVID-19 vaccines using wild-type nucleocapsid (N) and Spike (S) protein. We upgrade this strategy by one step further using clinically proven spike protein (but with delta and post-delta omicron mutations) and nucleocapsid peptides conferring T-cell immunity. As per the latest research nucleocapsid peptides are perfect immunological replacement of nucleocapsid protein. Therefore, peptide linking strategy is pursued (economic for cellular biosynthesis than whole protein). One envelope peptide with potent T-cell response is also chosen. This peptide is also functionally indispensable for the virus. All these peptides were clustered in our designed cytoplasmic domain separated by non-immunogenic helical linkers. We also propose the idea of introduction of any T-cell peptide similar to other Human Corona Viruses (HuCoV) in these linker regions whenever required. In addition to COVID, the same approach can be applied for any emergency or even long-term unsolved outbreaks of Influenza, Dengue and West Nile Virus etc. In this era of novelty as presented by subunit and nucleic acid vaccines, multiepitope strategies like this can help to combat multiple diseases successfully in real time to give hope for better future.

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“…To date, no data are available on SARS-CoV-2-directed T cell responses in cancer patients. In the meantime, multiple studies have identi ed the central role of SARS-CoV-2-speci c T cell responses for the clinical course of COVID-19 as well as for the development of long-term immunity (18)(19)(20)(21)(22)(23)(24)(25). This comprises evidence for potential pre-existing immunity mediated by T cells cross-reactive to human common cold coronaviruses (HCoV), which may provide a certain degree of protection against severe illness upon COVID-19 (18,19,21).…”

Section: Introductionmentioning

confidence: 99%

Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients

Bilich

Roerden²,

Maringer

et al. 2021

Preprint

Self Cite

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Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV‑2 immunity and to identify immunological parameters contributing to COVID-19 outcome. Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 cancer patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer patients, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T cell immunity as determinant for dismal outcome of COVID-19 in cancer patients.

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Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19

Cited by 4 publications

References 35 publications

Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults

Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults

De novodesign of anti-variant COVID-19 Vaccine

Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients

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