Modulation of innate immune responses by influenza-specific ovine polyclonal antibodies used for prophylaxis

PLoS One. 2014 Feb 28;9(2):e89674. doi: 10.1371/journal.pone.0089674. eCollection 2014.

Abstract

In the event of a novel influenza A virus pandemic, prophylaxis mediated by antibodies provides an adjunct control option to vaccines and antivirals. This strategy is particularly pertinent to unvaccinated populations at risk during the lag time to produce and distribute an effective vaccine. Therefore, development of effective prophylactic therapies is of high importance. Although previous approaches have used systemic delivery of monoclonal antibodies or convalescent sera, available supply is a serious limitation. Here, we have investigated intranasal delivery of influenza-specific ovine polyclonal IgG antibodies for their efficacy against homologous influenza virus challenge in a mouse model. Both influenza-specific IgG and F(ab')2 reduced clinical scores, body weight loss and lung viral loads in mice treated 1 hour before virus exposure. Full protection from disease was also observed when antibody was delivered up to 3 days prior to virus infection. Furthermore, effective prophylaxis was independent of a strong innate immune response. This strategy presents a further option for prophylactic intervention against influenza A virus using ruminants to generate a bulk supply that could potentially be used in a pandemic setting, to slow virus transmission and reduce morbidity associated with a high cytokine phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Immunity, Innate / immunology*
  • Influenza A virus / immunology
  • Influenza A virus / pathogenicity
  • Orthomyxoviridae Infections / immunology*
  • Sheep

Substances

  • Antibodies, Viral

Grants and funding

This study was supported in part by AB-Health, and funding from Murdoch University was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.