The lymphatic system and COVID-19 vaccines

Miyasaka, Masayuki

doi:10.3389/fimmu.2022.1041025

Cited by 7 publications

(5 citation statements)

References 57 publications

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“…Although all COVID-19 vaccines are based on the full-length S protein, the presentation of antigen-derived peptides is strikingly different -not only between protein-based and nucleic acid-based vaccines but also between mRNA (BNT) and vector (ChAd) vaccines. This in turn leads to different CD8+ and CD4+ T cell activation, which shapes the subsequent antibody response (77)(78)(79)(80). It is conceivable that the heterogeneity of current vaccine platforms negatively affects the comparability of binding assays that detect total antibodies directed against the same antigen.…”

Section: Discussionmentioning

confidence: 99%

Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination

Schest,

Langer,

Stiegler

et al. 2023

Front. Immunol.

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BackgroundQuantification of the SARS-CoV-2-specific immune response by serological immunoassays is critical for the management of the COVID-19 pandemic. In particular, neutralizing antibody titers to the viral spike (S) protein have been proposed as a correlate of protection (CoP). The WHO established the First International Standard (WHO IS) for anti-SARS-CoV-2 immunoglobulin (Ig) (NIBSC 20/136) to harmonize binding assays with the same antigen specificity by assigning the same unitage in binding antibody units (BAU)/ml.MethodIn this study, we analyzed the S1-specific antibody response in a cohort of healthcare workers in Germany (n = 76) during a three-dose vaccination course over 8.5 months. Subjects received either heterologous or homologous prime-boost vaccination with ChAdOx1 nCoV-19 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) or three doses of BNT162b2. Antibodies were quantified using three anti-S1 binding assays (ELISA, ECLIA, and PETIA) harmonized to the WHO IS. Serum levels of neutralizing antibodies were determined using a surrogate virus neutralization test (sVNT). Binding assays were compared using Spearman’s rank correlation and Passing–Bablok regression.FindingsAll assays showed good correlation and similar antibody kinetics correlating with neutralizing potential. However, the assays show large proportional differences in BAU/ml. ECLIA and PETIA, which detect total antibodies against the receptor- binding domain (RBD) within the S1 subunit, interact similarly with the convalescent plasma-derived WHO IS but differently with vaccine serum, indicating a high sensitivity to the IgG/IgM/IgA ratio.ConclusionAll three binding assays allow monitoring of the antibody response in COVID-19-vaccinated individuals. However, the assay-specific differences hinder the definition of a common protective threshold in BAU/ml. Our results highlight the need for the thoughtful use of conversion factors and consideration of method-specific differences. To improve the management of future pandemics and harmonize total antibody assays, we should strive for reference material with a well-characterized Ig isotype composition.

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Section: Discussionmentioning

confidence: 99%

Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination

Schest,

Langer,

Stiegler

et al. 2023

Front. Immunol.

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“…Administration of vaccines through intramuscular injection and mucosal surface adhesion represents the most successful medication targeting the lymphatic system, which is an indispensable tool for the prevention of infectious diseases such as the COVID-19 pandemic. 12,13 Since immune activation within LNs is central for efficient antitumor immunotherapy, targeted drug delivery to LNs holds great potential to enhance antitumor immune response via improving antigen presentation of antigen-presenting cells (APCs) for augmented T cell activation. 14,15 Unfortunately, a highly immunosuppressive TME in solid tumors may significantly defy any efforts of activating antitumor immunity within LNs.…”

Section: Introductionmentioning

confidence: 99%

“…LNs serve as the fundamental tissues of the immune system, making drug administration through the lymphatic system one of the direct immune activation routes. Administration of vaccines through intramuscular injection and mucosal surface adhesion represents the most successful medication targeting the lymphatic system, which is an indispensable tool for the prevention of infectious diseases such as the COVID-19 pandemic. , Since immune activation within LNs is central for efficient antitumor immunotherapy, targeted drug delivery to LNs holds great potential to enhance antitumor immune response via improving antigen presentation of antigen-presenting cells (APCs) for augmented T cell activation. , …”

Section: Introductionmentioning

confidence: 99%

Dual-Responsive Nanomedicine Activates Programmed Antitumor Immunity through Targeting Lymphatic System

Xiao,

Li,

Liang

et al. 2024

ACS Nano

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Effective antitumor immunotherapy depends on evoking a cascade of cancer-immune cycles with lymph nodes (LNs) as the initial sites for activating antitumor immunity, making drug administration through the lymphatic system highly attractive. Here, we describe a nanomedicine with dual responsiveness to pH and enzyme for a programmed activation of antitumor immune through the lymphatic system. The proposed nanomedicine can release the STING agonist diABZI-C2-NH 2 in the LNs' acidic environment to activate dendritic cells (DCs) and T cells. Then, the remaining nanomedicine hitchhikes on the activated T cells (PD-1 + T cells) through binding to PD-1, resulting in an effective delivery into tumor tissues owing to the tumor-homing capacity of PD-1 + T cells. The enzyme matrix metalloproteinase-2 (MMP-2) being enriched in tumor tissue triggers the release of PD-1 antibody (aPD-1) which exerts immune checkpoint blockade (ICB) therapy. Eventually, the nanomedicine delivers a DNA methylation inhibitor GSK-3484862 (GSK) into tumor cells, and then the latter combines with granzyme B (GZMB) to trigger tumor cell pyroptosis. Consequently, the pyroptotic tumor cells induce robust immunogenic cell death (ICD) enhancing the DCs maturation and initiating the cascading antitumor immune response. Study on a 4T1 breast tumor mouse model demonstrates the prominent antitumor therapeutic outcome of this nanomedicine through creating a positive feedback loop of cancer-immunity cycles including immune activation in LNs, T cell-mediated drug delivery, ICB therapy, and tumor cell pyroptosis-featured ICD.

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“…Lymphadenopathy, which refers to an abnormality in LN size and consistency, can occur due to various reasons, including bacterial, viral, or fungal infections, autoimmune disorders, and malignancies [ 2 ]. Reports have surfaced indicating the occurrence of lymphadenopathy after coronavirus disease 2019 (COVID-19) vaccination, which is thought to occur as the vaccine components enter the LNs through the lymphatic system and generate an immune reaction, causing proliferation of lymphocytes [ 3 ]. The S-specific TFH cell response in axillary LN fine-needle biopsies from 15 individuals in the clinical trial of the BNT162b2 vaccine could be interpreted as mechanistic evidence that lymphadenopathy can be induced as part of the normal immune response to vaccination [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…[2] Reports have surfaced indicating the occurrence of lymphadenopathy after COVID-19 vaccination, which is thought to occur as the vaccine components enter the LNs through the lymphatic system and generate an immune reaction, causing proliferation of lymphocytes. [3] The S-specific TFH cell response in axillary LN fine-needle biopsies from 15 individuals in the clinical trial of the BNT162b2 vaccine could be interpreted as mechanistic evidence that lymphadenopathy can be induced as part of the normal immune response to vaccination. [4] Furthermore, the observation of Sbinding germinal center B cells and plasmablasts in the draining LNs after a booster dose of the BNT162b2 vaccine provides the same rationale for lymphadenopathy due to the booster vaccination.…”

Section: Introductionmentioning

confidence: 99%

Risk of lymphadenopathy from SARS-CoV-2 vaccination in Korea: a self-controlled case series analysis

Kim,

Choi

et al. 2023

Epidemiol Health

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OBJECTIVES: To assess the risk of lymphadenopathy following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.METHODS: A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1-day to 42-day risk interval after coronavirus disease 2019 (COVID-19) vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval.RESULTS: The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% confidence interval [CI], 1.17 to 1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44 to 1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson’s comorbidity index <5, and those who received mRNA vaccines (mRNA-1273>BNT162b2). Within the 1-day to 42-day post-dose risk period, the relative risk was highest during the 1-day to 7-day post-dose period (1.59; 95% CI, 1.57 to 1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI.CONCLUSIONS: SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.

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The lymphatic system and COVID-19 vaccines

Cited by 7 publications

References 57 publications

Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination

Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination

Dual-Responsive Nanomedicine Activates Programmed Antitumor Immunity through Targeting Lymphatic System

Risk of lymphadenopathy from SARS-CoV-2 vaccination in Korea: a self-controlled case series analysis

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