Analysis of the Prevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Student Cohorts Reveals Low-Prevalence Types and a Decline in Binding Antibody Levels during the SARS-CoV-2 Pandemic

Wang, Xiaoyan; Kerkmann, Leonie; Hetzel, Mario; Windmann, Sonja; Trilling, Mirko; Zhang, Wenli; Ehrhardt, Anja; Bayer, Wibke

doi:10.1128/jvi.01133-22

Cited by 4 publications

(16 citation statements)

References 40 publications

(43 reference statements)

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“…All HAdV types were purified by a CaptoCore (Sigma-Aldrich, Taufkirchen, Germany) bead-based method adapted from [ 57 ], cesium chloride gradient ultracentrifugation or AdenoPack20 kit (Vivascience, Hannover, Germany). As reported before, the different purification methods did not influence the binding antibody ELISA results [ 54 ].…”

Section: Methodsmentioning

confidence: 64%

“…The HAdV types used in this study have been described in detail previously [ 54 ]. Briefly, we used 39 HAdV types: HAdV-A12, -A18, -A31, -B3, -B7, -B11, -B14, -B16, -B21, -B34, -B35, -B50, -C1, -C2, -C5, -C6, -D8, -D9, -D10, -D13, -D17, -D20, -D24, -D25, -D26, -D27, -D33, -D37, -D48, -D65, -D69, -D70, -D73, -D74, -D75, -D80, -E4, -F41, and -G52.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, we used 39 HAdV types: HAdV-A12, -A18, -A31, -B3, -B7, -B11, -B14, -B16, -B21, -B34, -B35, -B50, -C1, -C2, -C5, -C6, -D8, -D9, -D10, -D13, -D17, -D20, -D24, -D25, -D26, -D27, -D33, -D37, -D48, -D65, -D69, -D70, -D73, -D74, -D75, -D80, -E4, -F41, and -G52. Most HAdV were wild-type viruses, except for HAdV-B16, -B50, -D48, -D65, and -D69, where we used GFP and/or luciferase encoding vectors as described previously [ 54 ]. All HAdV types were purified by a CaptoCore (Sigma-Aldrich, Taufkirchen, Germany) bead-based method adapted from [ 57 ], cesium chloride gradient ultracentrifugation or AdenoPack20 kit (Vivascience, Hannover, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…HAdV types in a Belgian blood donor cohort [53]. We have ourselves recently performed an analysis of binding and neutralizing antibodies against 39 HAdV types in a cohort of young healthy adults [54], where we could identify a number of low-prevalent HAdV types mainly from species A, B, and D that may be promising candidates for future vaccine and gene therapy vector development. To expand on these findings, in the study presented here, we investigated the seroprevalence in patients suffering from different NMDs.…”

Section: Introductionmentioning

confidence: 99%

“…In many cases, the studies focused on only a small number of HAdV types, with the notable exceptions of a study of neutralizing antibodies against 33 HAdV types in young children in Italy [ 52 ] and the study of neutralizing antibodies against 51 HAdV types in a Belgian blood donor cohort [ 53 ]. We have ourselves recently performed an analysis of binding and neutralizing antibodies against 39 HAdV types in a cohort of young healthy adults [ 54 ], where we could identify a number of low-prevalent HAdV types mainly from species A, B, and D that may be promising candidates for future vaccine and gene therapy vector development. To expand on these findings, in the study presented here, we investigated the seroprevalence in patients suffering from different NMDs.…”

Section: Introductionmentioning

confidence: 99%

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Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders

Klann

Wang

Elfert

et al. 2022

Viruses

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High pre-existing antibodies against viral vectors reduce their functionality and may lead to adverse complications. To circumvent this problem in future gene therapy approaches, we tested the seroprevalence of a large range of human adenovirus types in patients with neuromuscular disorders (NMDs) to find appropriate viral vector candidates for gene replacement therapy for NMDs. Binding and neutralizing antibodies against 39 human adenovirus types were tested in the sera of 133 patients with NMDs and 76 healthy controls aged 17–92 years. The influence of age, sex, and NMDs on antibody levels was analyzed. The seroprevalence of different adenoviruses in the cohort varied widely. The highest levels of binding antibodies were detected against HAdV-D27, -C1, -D24, -D70, -B14, -C6, -D13, -B34, and -E4, whereas the lowest reactivity was detected against HAdV-F41, -A31, -B11, -D75, -D8, -D65, -D26, -D80, and ‑D17. The highest neutralizing reactivity was observed against HAdV-B3, -C2, -E4, -C1, -G52, -C5, and -F41, whereas the lowest neutralizing reactivity was observed against HAdV-D74, -B34, -D73, -B37, -D48, -D13, -D75, -D8, -B35, and -B16. We detected no influence of sex and only minor differences between different age groups. Importantly, there were no significant differences between healthy controls and patients with NMDs. Our data show that patients with NMDs have very similar levels of binding and neutralizing antibodies against HAdV compared to healthy individuals, and we identified HAdV-A31, -B16, -B34, -B35, -D8, -D37, -D48, -D73, -D74, -D75, and -D80 as promising candidates for future vector development due to their low binding and neutralizing antibody prevalence.

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Section: Methodsmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders

Klann

Wang

Elfert

et al. 2022

Viruses

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HDAd6/35++ - A new helper-dependent adenovirus vector platform for in vivo transduction of hematopoietic stem cells

Wang¹,

Georgakopoulou²,

Zhang³

et al. 2023

Molecular Therapy - Methods & Clinical Development

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Adenovirus-specific T cells in adults are frequent, cross-reactive to common childhood adenovirus infections and boosted by adenovirus-vectored vaccines

Mukhopadhyay,

Lambisia,

Hoang

et al. 2024

Preprint

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Human adenoviruses (HAdVs) cause diverse disease presentations as pathogens, and are also used as viral vectors for vaccines and gene therapy products. Preexisting adaptive immune responses to HAdV are known to influence symptom severity, viral clearance and the success of viral vectored products. Of note, approximately 50% of the UK's adult population has received at least one dose of a chimpanzee adenovirus vectored SARS-CoV-2 vaccine (ChAdOx1) since January 2021. We used FluoroSpot analysis to quantify the interferon gamma (IFNg) and interleukin-2 (IL2) responses of healthy blood donors to HAdV species A, B, C, D and F and chimpanzee adenovirus Y25, related to HAdV species E. We find that cellular immune responses to multiple species of human adenovirus are ubiquitous among healthy adult blood donors, and that stimulating PBMC with whole hexon peptide libraries induces a significantly greater IFNg and IL2 response than using selected peptide pools alone. We then compared the cellular immune responses of ChAdOx1 recipients and control donors using PBMC collected in 2021, and found that homotypic and heterotypic IFNg responses were significantly boosted in ChAdOx1 recipients but not controls. Finally, we show that in PBMC derived from blood donors, IFNg responses are made to both conserved and variable regions of the hexon protein. Future vaccination campaigns using adenoviral vectored vaccines will need to account for the pre-existing exposure of recipients to both circulating HAdVs and vaccines such as ChAdOx1, which convey polyfunctional antiviral T cell responses to even low seroprevalence HAdV types.

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Analysis of the Prevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Student Cohorts Reveals Low-Prevalence Types and a Decline in Binding Antibody Levels during the SARS-CoV-2 Pandemic

Cited by 4 publications

References 40 publications

Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders

Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders

HDAd6/35++ - A new helper-dependent adenovirus vector platform for in vivo transduction of hematopoietic stem cells

Adenovirus-specific T cells in adults are frequent, cross-reactive to common childhood adenovirus infections and boosted by adenovirus-vectored vaccines

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