COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity

Kroemer, Marie; Spehner, Laurie; Vettoretti, Lucie; Bouard, Adeline; Eberst, Guillaume; Floury, Sébastien Pili; Capellier, Gilles; Lepiller, Quentin; Orillard, Émeline; Mansi, Laura; Clairet, Anne-Laure; Westeel, Virginie; Limat, Samuel; Dubois, Maxime; Malinowski, Léa; Bohard, Louis; Borg, Christophe; Chirouze, Catherine; Bouiller, Kévin

doi:10.1016/j.jinf.2020.08.036

Cited by 36 publications

(36 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, the frequencies of SARS‐CoV‐2–specific T cells were in fact in the same range as those observed in convalescent patients from predominantly mild 13,18 or severe COVID‐19 11 . Interestingly, Kroemer et al observed higher numbers of IFNγ‐producing T cells reactive to N peptide pool in patients with mild illness as compared to patients with severe pneumonia, 21 to 53 days following symptoms onset 19 . Such preliminary observations in convalescent individuals suggest that the amplitude of the T cell response may not directly impact disease severity.…”

Section: Discussionsupporting

confidence: 85%

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic

Candon

Guerrot

Drouot

et al. 2021

American Journal of Transplantation

View full text Add to dashboard Cite

Immunosuppressed organ‐transplanted patients are considered at risk for severe forms of COVID‐19. Moreover, exaggerated innate and adaptive immune responses might be involved in severe progression of the disease. However, no data on the immune response to SARS‐CoV‐2 in transplanted patients are currently available. Here, we report the first assessment of antibody and T cell responses to SARS‐CoV‐2 in 11 kidney‐transplanted patients recovered from RT‐PCR–confirmed (n = 5) or initially suspected (n = 6) COVID‐19. After reduction of immunosuppressive therapy, RT‐PCR–confirmed COVID‐19 transplant patients were able to mount vigorous antiviral T cell and antibody responses, as efficiently as two nontherapeutically immunosuppressed COVID‐19 patients on hemodialysis. By contrast, six RT‐PCR–negative patients displayed no antibody response. Among them, three showed very low numbers of SARS‐CoV‐2–reactive T cells, whereas no T cell response was detected in the other three, potentially ruling out COVID‐19 diagnosis. Low levels of T cell reactivity to SARS‐CoV‐2 were also detected in seronegative healthy controls without known exposure to the virus. These results suggest that during COVID‐19, monitoring both T cell and serological immunity might be helpful for the differential diagnosis of COVID‐19 but are also needed to evaluate a potential role of antiviral T cells in the development of severe forms of the disease.

show abstract

Section: Discussionsupporting

confidence: 85%

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic

Candon

Guerrot

Drouot

et al. 2021

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…T cells are critical for elimination of SARS-CoV infection. 36,[74][75][76][77][78] Here, hAd5 expressed S and N elicited strong antigen-specific IFN-g, but virtually no IL-4 secretion from T cells of previously infected SARS-CoV-2 patients, pointing to Th1 dominance. Antiviral Th1 cytokine responses eliminate a variety of viruses from infected hosts 79 including the virus closely related to SARS-CoV-2, SARS-CoV.…”

Section: Discussionmentioning

confidence: 89%

Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T Cell Recall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells from Patients Previously Infected with SARS-CoV-2

Sieling

Zakin

Shin

et al. 2020

Preprint

View full text Add to dashboard Cite

To address the need for a safe, efficacious vaccine against SARS-CoV-2 infection with the critical properties of enabling both blocking viral entry into cells and clearing virus from cells already infected, we have developed a bivalent, human adenovirus serotype 5 (hAd5) SARS-CoV-2 S-Fusion + N-ETSD vaccine that is currently in clinical testing. This vaccine uses the next-generation hAd5 [E1-, E2b-, E3-] platform previously used successfully in cancer patients with pre-existing adenovirus immunity, engineered to express both SARS-CoV-2 spike (S) protein modified to improve the generation of neutralizing antibodies to block entry of the virus, and nucleocapsid (N) protein with an Enhanced T cell Stimulation Domain (ETSD) to activate CD4+ and CD8+ T cells to clear the virus and block replication by killing infected cells. The targeting of N to endosomes and lysosomes to enhance CD4+ and CD8+ T-cell responses distinguishes our vaccine. In our previously reported pre-clinical studies we showed that in mice, the hAd5 S-Fusion + N-ETSD vaccine elicits both humoral and T-cell responses that are robust and T helper cell 1 (Th1) dominant. Here we report that the hAd5 S-Fusion + N-ETSD vaccine is recognized by anti-sera and T cells from previously SARS-CoV-2 infected patients, and that the presence of N is vital for T-cell recall. The findings presented herein: i. demonstrate specific recognition of hAd5 S-Fusion + N-ETSD infected cells by plasma antibodies from previously SARS-CoV-2 infected patients, but not antibodies from virus-naive subjects; ii. show enhanced binding of plasma SARS-CoV-2 antibodies from previously infected patients to monocyte-derived dendritic cells (MoDCs) expressing the hAd5 S-Fusion + N-ETSD vaccine as compared to hAd5 S-Fusion alone; iii. reveal N-ETSD localizes to vesicles associated with MHC class II antigen presentation, including endosomes, lysosomes, and autophagosomes in MoDCs; iv. demonstrate endosome/lysosome-targeted N-ETSD elicits higher interferon-gamma T-cell responses than cytoplasm-localized N; and v. N-ETSD alone or in the hAd5 S-Fusion + N-ETSD construct induces both CD4+ and CD8+ T cell memory recall. This recognition of hAd5 S-Fusion + N-ETSD vaccine antigens by T cells from previously SARS-CoV-2 infected patients, together with the ability of this vaccine candidate to elicit de novo immune responses in naive mice suggests that it re-capitulates the natural immune response to SARS-CoV-2 to activate both B and T cells towards viral neutralization and recognition of infected cells, critical for prevention of COVID-19 disease. Intriguingly, our hAd5 S-Fusion + N-ETSD T-cell biased vaccine has the potential to not only provide protection for uninfected individuals, but also to be utilized as a therapeutic for already infected patients to induce rapid clearance of the virus by activating T cells to kill the virus-infected cells, thereby reducing viral replication and lateral transmission.

show abstract

“…All patients were enrolled after the signature of informed consent in accordance with the French regulation. Three cohorts of patients were enrolled: i) patients with mild illness COVID-19 infection without cancer, whose clinical parameters have been described elsewhere [ 11 ] ii) patients with solid tumors, iii) patients with hematological malignancies. The analyzed population was diagnosed with COVID-19 between March 10 and May 20.…”

Section: Methodsmentioning

confidence: 99%

Study of the SARS-CoV-2-specific immune T-cell responses in COVID-19-positive cancer patients

Mansi

Spehner

Daguindau

et al. 2021

European Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Background Cancer patients are considered as highly vulnerable to COVID-19 pandemic. However, delaying cancer specific therapies could have a deleterious effect on survival. The potential suppressive effects of chemotherapies or cancer-related microenvironment raised the question on how cancer patients’ immune system responds to SARS-CoV-2 virus. Methods We have started a prospective monocentric trial entitled COV-CREM (NCT04365322) on April 2020. The primary trial objective was to assess specific immune response’s intensity and diversity to SARS-CoV-2 for infected patients. Results In this study, we showed that cancer patients (28 solid tumors, 11 hematological malignancies) exposed to SARS-CoV-2 produced high rate of specific antibodies, as observed in patients without cancer history (n=29). However, our results highlight a lack in the generation of T-cell responses against CoV-N, M and S proteins from SARS-CoV-2 virus, suggesting that cancer patients failed to mount a protective T-cell immunity. Nevertheless, SARS-CoV-2 infection did not impair established immune memory since specific responses against common viruses was not hampered in cancer patients. Conclusion Given the severity and the unknown evolution of the ongoing COVID-19 pandemic, it is of fundamental importance to integrate cancer patients in vaccination programs.

show abstract

COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity

Abstract: COVID-19 patients display distinct SARS-CoV-2 specific T-cell responses according to disease severity

Cited by 36 publications

References 7 publications

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic

Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T Cell Recall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells from Patients Previously Infected with SARS-CoV-2

Study of the SARS-CoV-2-specific immune T-cell responses in COVID-19-positive cancer patients

Contact Info

Product

Resources

About