Deciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response

Pérez-Gómez, Alberto; Gasca-Capote, M Carmen; Vitallé, Joana; Ostos, Francisco José; Serna-Gallego, Ana; Trujillo‐Rodríguez, María; Muñoz-Muela, Esperanza; Giraldez-Perez, Teresa; Praena-Segovia, Juliav; Navarro-Amuedo, María Dolores; Paniagua-García, María; García-Gutiérrez, Manuel; Aguilar‐Guisado, Manuela; Rivas‐Jeremías, Inmaculada; Jiménez-León, María Reyes; Bachiller, Sara; Fernández-Villar, Alberto; Pérez-González, Alexandre; Gutiérrez‐Valencia, Alicia; Benhnia, Mohammed Rafii‐El‐Idrissi; Weiskopf, Daniela; Sette, Alessandro; López‐Cortés, Luis F.; Poveda, Eva; Ruiz‐Mateos, Ezequiel

doi:10.1101/2021.12.28.474325

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…Our results also showed that Clec9A-RBD single dose immunization induced a potent and sustained antigen-specific poly-functional TH1 cellular response, consistent with our previous studies that targeted antigens to Clec9A-expressing cDC1 [16,42]. Poly-functional T cells have been proposed to represent a correlate of protection in other infectious diseases such as dengue and this feature is applicable towards COVID-19 as well [43][44][45]. Furthermore, Clec9A-RBD was able to elicit robust RBD-specific T cell memory that could be recalled 6-12 months postimmunization.…”

Section: Discussionsupporting

confidence: 90%

Single shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad and durable systemic and mucosal immune responses

Cheang

Tan

Purushotorman

et al. 2023

Preprint

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Current COVID-19 vaccines face certain limitations, which include waning immunity, immune escape by SARS-CoV-2 variants, limited CD8+ cellular response, and poor induction of mucosal immunity. Here, we engineered a Clec9A-RBD antibody construct that delivers the Receptor Binding Domain (RBD) from SARS-CoV-2 spike protein to conventional type 1 dendritic cells (cDC1). We showed that single dose immunization with Clec9A-RBD induced high RBD-specific antibody titers with a strong T-helper 1 (TH1) isotype profile and exceptional durability, whereby antibody titers were sustained for at least 21 months post-vaccination. Uniquely, affinity maturation of the antibody response was observed over time, as evidenced by enhanced neutralization potency and breadth across the sarbecovirus family. Consistently and remarkably, RBD-specific T-follicular helper cells and germinal center B cells were still detected at 12 months post-immunization. Increased antibody-dependent cell-mediated cytotoxicity (ADCC) activity of the immune sera was also measured over time with comparable efficacy against ancestral SARS-CoV-2 and variants, including Omicron. Furthermore, Clec9A-RBD immunization induced a durable poly-functional TH1-biased cellular response that was strongly cross-reactive against SARS-CoV-2 variants, including Omicron, and with robust CD8+ T cell signature. Lastly, Clec9A-RBD single dose systemic immunization primed effectively RBD-specific cellular and humoral mucosal immunity in lung. Taken together, Clec9A-RBD immunization has the potential to trigger robust and sustained, systemic and mucosal immune responses against rapidly evolving SARS-CoV2 variants.

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Section: Discussionsupporting

confidence: 90%

Single shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad and durable systemic and mucosal immune responses

Cheang

Tan

Purushotorman

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The SARS-CoV-2 specific CD4+ and CD8+ T cells were more related to protective immunity and immune memory against re-infection [16]. A recent study found that convalescent patients presented robust SARS-CoV-2 specific T cell response after seven-month infection [45]. Longer follow-up studies are needed to further understand mechanisms of protective adaptive immune responses to COVID-19.…”

Section: Discussionmentioning

confidence: 98%

A one-year follow-up study on dynamic changes of leukocyte subsets and virus-specific antibodies of patients with COVID-19 in Sichuan, China

Xu¹,

Zhao²,

Lan³

et al. 2022

Int. J. Med. Sci.

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Background: SARS-CoV-2 infection causes immune response and produces protective antibodies, and these changes may persist after patients discharged from hospital. Methods: This study conducted a one-year follow-up study on patients with COVID-19 to observe the dynamic changes of circulating leukocyte subsets and virus-specific antibodies. Results: A total of 66 patients with COVID-19 and 213 healthy patients with inactivated SARS-CoV-2 vaccination were included. The virus-specific total antibody, IgG and IgM antibody of patients after one year of recovery were higher than those of healthy vaccinated participants (94.13 vs 4.65, 2.67 vs 0.44, 0.09 vs 0.06, respectively) (P < 0.001). Neutrophil count (OR = 1.73, 95% CI: 1.10-2.70, P = 0.016) and neutrophil-to-lymphocyte ratio (OR = 1.59, 95% CI: 1.05-2.41, P = 0.030) at discharge were the influencing factors for the positivity of virus-specific IgG antibody in patients after one year of recovery. The counts of CD4+ and CD8+ T, B and NK cells increased with the time of recovery, and remained basically stable from 9 to 12 months after discharge. After 12 months, the positivity of IgG antibody was 85.3% and IgM was 11.8%, while the virus-specific antibody changed dynamically in patients within one year after discharge. Conclusions: The SARS-CoV-2 specific antibody of recovered patients showed dynamic fluctuation after discharge, while the leukocyte subsets gradually increased and basically stabilized after 9 months.

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“…1.5 × 10 6 PBMCs incubated with the proportional amount of DMSO were included in each experiment as a negative control. The stimulation was performed in the presence of 10 µg/mL of brefeldin A (Sigma Chemical Co) and 0.7 µg/mL of monensin (Golgi Stop, BD Biosciences) protein transport inhibitors, anti-CD107a-BV650 (clone H4A3; BD Biosciences) monoclonal antibody and purified CD28 (clone CD28.2) and CD49d (clone 9F10) (BD Biosciences) as previously described (67,68). Intracellular cytokines and cytotoxicity markers were analyzed by multiparametric flow cytometry.…”

Section: Sars-cov-2 Specific T Cell Responsementioning

confidence: 99%

Immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in aged people

Vitallé¹,

Pérez-Gómez²,

Ostos³

et al. 2022

JCI Insight

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The immune factors associated with impaired SARS-CoV-2 vaccine response in the elderly are mostly unknown. We studied >60 and <60 years old people vaccinated with SARS-CoV-2 BNT162b2 mRNA before and after the first and second dose. Aging was associated with a lower anti-RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2 specific T cell response. The dramatic decrease in thymic function in aged people with >60 years of age, which fueled alteration in T cell homeostasis, and lower CD161+ T cell levels were associated with decreased T cell response two months after vaccination. Additionally, a deficient dendritic cell (DC) homing, activation and Toll like receptor (TLR)-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the >60 years old group, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes.

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Deciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response

Cited by 4 publications

References 40 publications

Single shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad and durable systemic and mucosal immune responses

Single shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad and durable systemic and mucosal immune responses

A one-year follow-up study on dynamic changes of leukocyte subsets and virus-specific antibodies of patients with COVID-19 in Sichuan, China

Immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in aged people

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