Seroprevalence of Human Adenovirus Type 5 Neutralizing Antibody in Common Marmosets Determined by a New Set of Two Assays

Viral Immunol. 2019 Oct;32(8):348-354. doi: 10.1089/vim.2019.0054. Epub 2019 Aug 21.

Abstract

Preexisting neutralizing antibody (NAb) against human adenovirus serotype 5 (AdHu5) can reduce the immunogenicity of AdHu5 vector-based vaccine, thus inhibiting the host's immune response and utility of other homologous vectors. Common marmoset (Callithrix jacchus), a small new world primate, has attracted considerable attention for its potential as a preclinical research model of vaccine development. However, the prevalence of anti-AdHu5 NAb activity in common marmosets bred in China remains unknown. A recombinant adenovirus expressing luciferase and Zs Green reporter genes were constructed to detect NAb against rAdHu5 by flow cytometry (FCM) and chemiluminescence (CL) assay. Five of 25 marmosets (20%) presented AdHu5 NAb detectable by FCM. Four animals had low titer (1/16), while the fifth one reached 1/64. While by CL assay, 7 of 25 (28%) marmosets were anti-AdHu5 NAb positive. Four animals, two of whom were negative by FCM, also had low titer NAb (1/16), suggesting assay discrepancy at low levels. Two marmosets, 1/32 titer by CL, were at 1/16 by FCM. A single animal showed a high titer with both assays (1/128 and 1/64 by CL and FCM, respectively). The CL method was simpler, more sensitive, accurate, and stable. The low prevalence of preexisting anti-AdHu5 NAb in marmosets provides important background information on the feasibility and applicability of using marmosets as a preclinical research model for vaccine development.

Keywords: adenovirus type 5; common marmoset; preexisting neutralizing antibody; vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae Infections / blood
  • Adenoviridae Infections / immunology*
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Callithrix / immunology*
  • Flow Cytometry
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • Luminescent Measurements
  • Luminescent Proteins / genetics
  • Seroepidemiologic Studies
  • Serogroup

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Luminescent Proteins