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

Klann, Patrick Julian; Wang, Xiaoyan; Elfert, Anna; Zhang, Wenli; Köhler, Cornelia; Güttsches, Anne‐Katrin; Jacobsen, Frank; Weyen, Ute; Roos, Andreas; Ehrke‐Schulz, Eric; Ehrhardt, Anja; Vorgerd, Matthias; Bayer, Wibke

doi:10.3390/v15010079

Cited by 10 publications

(12 citation statements)

References 82 publications

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“…The remaining four donors were seronegative. This is broadly in line with binding antibody data collected in Germany 27,28 , where binding antibody levels were higher for genotype C1 than C5, and for previous serology surveys conducted in Europe 26 . This may also mirror the significant post-COVID reduction in binding antibody levels seen in German healthy serum donors between 2019 and 2021 28 , but the numbers presented here are small.…”

Section: Serological Responses To Adenovirus C5 Are Relatively Uncommonsupporting

confidence: 90%

“…The variable pool included peptides which showed variation within species A genotypes. In a post-SARS-CoV-2 emergence sample of donor serum from Germany, binding antibody responses to A12 were higher on average than responses to other species A genotypes, suggesting A12 was a suitable and seroprevalent representative of adaptive immune responses to species A adenoviruses in a post-pandemic population 27 .…”

Section: Resultsmentioning

confidence: 93%

“…We note a significant dichotomy between the high frequency of T cell responses to different adenovirus species (Figure 2), and the relatively small frequency of donors with detectable binding antibody levels to HAdV-C5 (Figure 1). Recent data from healthy donors in Germany 27,28 suggests that this may be because that the majority of donors have low-level circulating binding antibody responses to C5, represented by low OD values. We speculate that ELISA-based serological analysis of adenovirus binding antibody responses may not be sufficiently sensitive to establish past adenovirus infection history and immunity on a per-genotype level.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Serological Responses To Adenovirus C5 Are Relatively Uncommonsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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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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“…It is possible that the neutralizing seropositive properties of human sera in Prachuap Khiri Khan were a result of cross-neutralization with the other macaque-borne HAdV-G. In a study in which pre-existing antibodies against several adenovirus genotypes were tested, high neutralizing reactivity and seropositivity against various adenoviruses, i.e., HAdV-B, HAdV-C, HAdV-E, HAdV-G, and HAdV-F, were observed in human sera [ 56 ]. Pre-existing adenoviral antibodies could be a source of cross-neutralization.…”

Section: Discussionmentioning

confidence: 99%

A Novel Simian Adenovirus Associating with Human Adenovirus Species G Isolated from Long-Tailed Macaque Feces

Kosoltanapiwat,

van der Hoek,

Kinsella

et al. 2023

Viruses

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Metagenomics has demonstrated its capability in outbreak investigations and pathogen surveillance and discovery. With high-throughput and effective bioinformatics, many disease-causing agents, as well as novel viruses of humans and animals, have been identified using metagenomic analysis. In this study, a VIDISCA metagenomics workflow was used to identify potential unknown viruses in 33 fecal samples from asymptomatic long-tailed macaques (Macaca fascicularis) in Ratchaburi Province, Thailand. Putatively novel astroviruses, enteroviruses, and adenoviruses were detected and confirmed by PCR analysis of long-tailed macaque fecal samples collected from areas in four provinces, Ratchaburi, Kanchanaburi, Lopburi, and Prachuap Khiri Khan, where humans and monkeys live in proximity (total n = 187). Astroviruses, enteroviruses, and adenoviruses were present in 3.2%, 7.5%, and 4.8% of macaque fecal samples, respectively. One adenovirus, named AdV-RBR-6-3, was successfully isolated in human cell culture. Whole-genome analysis suggested that it is a new member of the species Human adenovirus G, closely related to Rhesus adenovirus 53, with evidence of genetic recombination and variation in the hexon, fiber, and CR1 genes. Sero-surveillance showed neutralizing antibodies against AdV-RBR-6-3 in 2.9% and 11.2% of monkeys and humans, respectively, suggesting cross-species infection of monkeys and humans. Overall, we reported the use of metagenomics to screen for possible new viruses, as well as the isolation and molecular and serological characterization of the new adenovirus with cross-species transmission potential. The findings emphasize that zoonotic surveillance is important and should be continued, especially in areas where humans and animals interact, to predict and prevent the threat of emerging zoonotic pathogens.

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“…Thus, it is highly desirable to enlarge the repertoire of effective AdV-based vaccine vectors for future vaccine development and epidemic preparedness. Toward this goal, we have investigated in previous studies the seroprevalence of 39 HAdV types in a cohort of medical students ( 32 ) and in a cohort of patients with neuromuscular disease ( 33 ) and identified rare HAdV types with significantly lower seroprevalence compared to HAdV-C5. In the study presented here, we aimed to characterize the same broad range of 39 HAdV types with regard to their immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8+ T cell proliferation capacity for the identification of favorable immunization vector candidates

Wang,

Hetzel,

Zhang

et al. 2023

Front. Immunol.

Self Cite

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For the development of new adenovirus (AdV)-based vectors, it is important to understand differences in immunogenicity. In a side-by-side in vitro analysis, we evaluated the effect of 40 AdV types covering human AdV (HAdV) species A through G on the expression of 11 activation markers and the secretion of 12 cytokines by AdV-transduced dendritic cells, and the effect on CD8+ T cell proliferation capacity. We found that the expression of activation markers and cytokines differed widely between the different HAdV types, and many types were able to significantly impair the proliferation capacity of CD8+ T cells. Univariate and multivariate regression analyses suggested an important role of type I interferons in mediating this suppression of CD8+ T cells, which we confirmed experimentally in a proliferation assay using a type I interferon receptor blocking antibody. Using Bayesian statistics, we calculated a prediction model that suggests HAdV types HAdV-C1, -D8, -B7, -F41, -D33, -C2, -A31, -B3 and -D65 as the most favorable candidates for vaccine vector development.

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

Cited by 10 publications

References 82 publications

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

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

A Novel Simian Adenovirus Associating with Human Adenovirus Species G Isolated from Long-Tailed Macaque Feces

Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8+ T cell proliferation capacity for the identification of favorable immunization vector candidates

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