The Presence of Antibody-Dependent Cell Cytotoxicity–Mediating Antibodies in Kaposi Sarcoma–Associated Herpesvirus–Seropositive Individuals Does Not Correlate with Disease Pathogenesis or Progression

Poppe, Lisa K.; Wood, Charles; West, John T.

doi:10.4049/jimmunol.2000489

Cited by 8 publications

(10 citation statements)

References 46 publications

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“…KS patients and asymptomatic KSHV-infected individuals were recruited from Zambia and Tanzania, as described previously [17][18][19][20]. Briefly, informed consent was obtained, whole blood samples were collected in EDTA tubes (BD), and plasma was isolated by centrifugation (545xg for 15 minutes).…”

Section: Sample Collectionmentioning

confidence: 99%

Antibody epitope profiling of the KSHV LANA protein using VirScan

et al. 2022

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The humoral antibody response against Kaposi sarcoma-associated herpesvirus (KSHV) in infected individuals has been characterized demonstrating the latency-associated nuclear antigen (LANA) as the most antigenic KSHV protein. Despite the antigenicity of the protein, specific LANA epitopes have not been systematically characterized. Here, we utilized a bacteriophage T7 library, which displays 56-amino acid KSHV LANA peptides with 28-amino acid overlap (VirScan), to define those epitopes in LANA targeted by antibodies from a cohort of 62 sub-Saharan African Kaposi Sarcoma (KS) patients and 22 KSHV-infected asymptomatic controls. Intra- and inter-patient breadth and magnitude of the anti-LANA responses were quantified at the peptide and amino acid levels. From these data, we derived a detailed epitope annotation of the entire LANA protein, with a high-resolution focus on the N- and C-termini. Overall, the central repeat region was highly antigenic, but the responses to this region could not be confidently mapped due to its high variability. The highly conserved N-terminus was targeted with low breadth and magnitude. In a minority of individuals, antibodies specific to the nuclear localization sequence and a portion of the proline-rich regions of the N-terminus were evident. In contrast, the first half of the conserved C-terminal domain was consistently targeted with high magnitude. Unfortunately, this region was not included in LANA partial C-terminal crystal structures, however, it was predicted to adopt predominantly random-coil structure. Coupled with functional and secondary structure domain predictions, VirScan revealed fine resolution epitope mapping of the N- and C-terminal domains of LANA that is consistent with previous antigenicity studies and may prove useful to correlate KSHV humoral immunity with pathogenesis.

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Section: Sample Collectionmentioning

confidence: 99%

Antibody epitope profiling of the KSHV LANA protein using VirScan

et al. 2022

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“… 5 The importance of Fc-mediated ADCC functions in both protection and pathogenesis have been recently reported for various infectious pathogens. 6 – 9 ADCC-inducing human immunodeficiency virus (HIV)-specific antibodies were identified as a key correlate of protection in the RV144 HIV vaccine trial. 10 ADCC by engaging the Fc effector on NK cells or phagocytes also contributes to prevention against several viral infections including Dengue fever and Ebola.…”

Section: Introductionmentioning

confidence: 99%

Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients

Wang

Zhang

et al. 2021

Sig Transduct Target Ther

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Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11–20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.

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“…This process depends on the isotype of antibodies produced during the immune response. For example, in humans IgG1 and in mice IgG2a or the analogous IgG2c antibodies are key players in facilitating ADCC (21)(22)(23). Therefore, we next aimed to understand whether immunization with MERS SClamp formulated with different adjuvants would affect the isotype of the antibody response (Figures 2A-D).…”

Section: Vaccine-induced Antibody Responses Vary With Potential For A...mentioning

confidence: 99%

Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine

et al. 2022

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Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either (i) aluminium hydroxide, (ii) SWE, a squalene-in-water emulsion, (iii) SQ, a squalene-in-water emulsion containing QS21 saponin, (iv) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); (v) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, (vi) or LMQ, neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP. All adjuvanted formulations induced elevated antibody titers which where greatest for QS21-containing formulations. These had elevated neutralization capacity and induced higher frequencies of IFNƔ and IL-2-producing CD4+ and CD8+ T cells. Additionally, LMQ-containing formulations skewed the antibody response towards IgG2b/c isotypes, allowing for antibody-dependent cellular cytotoxicity. This study highlights the utility of side-by-side adjuvant comparisons in vaccine development.

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The Presence of Antibody-Dependent Cell Cytotoxicity–Mediating Antibodies in Kaposi Sarcoma–Associated Herpesvirus–Seropositive Individuals Does Not Correlate with Disease Pathogenesis or Progression

Cited by 8 publications

References 46 publications

Antibody epitope profiling of the KSHV LANA protein using VirScan

Antibody epitope profiling of the KSHV LANA protein using VirScan

Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients

Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine

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