Neutralizing Antibody Against Infectious Canine Hepatitis Virus in Veterinary Workers'Sera (ICHV)

By the time we are adolescents most of us have been in contact with several of the >50 human adenovirus (HAd) serotypes. These common subclinical infections lead to an efficient anti-adenovirus cross-reacting adaptive immunity. During gene therapy, the ubiquitous anti-adenovirus humoral response and complement activation will modify and dictate vector biodistribution, as well as the response to the virion and transgene(s). In this study, we assayed the interactions of a xenogenic adenovirus derived from canine serotype 2 (CAV-2) with naturally occurring human antibodies (Abs) and the complement system. In our cohort, we found class G immunoglobulins (Igs) that recognized the intact CAV-2 virion and the external virion proteins. However, the majority of donors had low or no neutralizing Abs, class A, or class M Igs. Purified anti-HAd serotype 5 Abs also recognized CAV-2 virion proteins. In addition, in spite of the presence of anti-CAV-2 IgGs, CAV-2 poorly activated the classical and alternative complement cascades. This atypical response was due to a block upstream of the component 3 (C3) convertase and interplay between the component 1 (C1) inhibitor, the C1q-C1r2-C1s2 complex and CAV-2. Our data demonstrate that some xenogenic adenovirus vectors, like CAV-2, could lead to notably different outcomes following systemic delivery.

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Neutralizing Antibody Against Infectious Canine Hepatitis Virus in Veterinary Workers'Sera (ICHV)

Cited by 3 publications

References 2 publications

Serological evidence of human adenovirus infections in animals

Serological evidence of human adenovirus infections in animals

Incomplete human adenovirus replication in canine tumour cells and serological evidence of infections in tumour-bearing canine pets

Interactions Between Human Plasma Components and A Xenogenic Adenovirus Vector: Reduced Immunogenicity During Gene Transfer

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