High-Throughput Screening for the Prevalence of Neutralizing Antibodies against Human Adenovirus Serotype 5

Author:

Wettengel Jochen M.123ORCID,Naka Hiroaki4ORCID,Dissen Gregory A.5,Torgerson Jeffrey5,Pounder Michelle5,Mueller Simon F.6ORCID,Mueller Elisabeth6,Hagen Philipp2,Brandt Micah1,Protzer Ulrike23ORCID,Burwitz Benjamin J.1ORCID

Affiliation:

1. Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA

2. Institute of Virology, Technical University of Munich, 81675 Munich, Germany

3. German Center for Infection Research, Munich Partner Site, 81675 Munich, Germany

4. Division of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA

5. Molecular Virology Core, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA

6. LABOKLIN GmbH, 97688 Bad Kissingen, Germany

Abstract

Adenoviral vectors based on the human adenovirus species C serotype 5 (HAdV-C5) are commonly used for vector-based gene therapies and vaccines. In the preclinical stages of development, their safety and efficacy are often validated in suitable animal models. However, pre-existing neutralizing antibodies may severely influence study outcomes. Here, we generated a new HAdV-C5-based reporter vector and established a high-throughput screening assay for the multivalent detection of HAdV-C5-neutralizing antibodies in serum. We screened the sera of rhesus macaques at different primate centers, and of rabbits, horses, cats, and dogs, showing that HAdV-C5-neutralizing antibodies can be found in all species, albeit at different frequencies. Our results emphasize the need to prescreen model animals in HAdV-C5-based studies.

Funder

NIH

DAAD Post-Doctoral Research Fellowship

German Center for Infection Research

Publisher

MDPI AG

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