Prophylaxis with broadly neutralizing monoclonal antibodies CR6261 and CR9114 protects mice against lethal H2 influenza virus challenge

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Authors

• TC Sutton
• E Lamirande
• M Rehman
• GJ Weverling
• J Goudsmit
• K Subbarao

Abstract

Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused pandemics in the last century. H2 influenza viruses represent a pandemic threat because they continue to circulate in wild birds, and an increasing proportion of the human population lack strain specific immunity. In the event of a pandemic, anti-viral agents are the primary treatment, however, broadly neutralizing monoclonal antibodies may be useful for prophylaxis and treatment. The monoclonal antibodies, CR6261 and CR9114, have been shown to protect mice from infection with H1N1 and H5N1, and H1N1, H3N2, and influenza B viruses, respectively. We evaluated the effectiveness of CR6261 and CR9114 against two H2 viruses A/Ann Arbor/6/1960 (H2N2) [A/AA] and A/swine/MO/4296424/06 (H2N3) [Sw06] that are lethal in mice. In vitro neutralization assays showed that CR6261 neutralized both H2 viruses, while CR9114 only neutralized Sw06. For an in vivo assessment, BALB/c mice were treated with CR6261 or CR9114 (0, 1.7, 5, or 15 mg/kg via i.p injection) and challenged 24 hours later with 25 median lethal doses (MLD50) of A/AA or Sw06. Following challenge, all mice lost weight, with more substantial weight loss observed at lower antibody doses. However, both antibodies provided complete protection from lethality at doses of 5 mg/kg or higher. At the 1.7 mg/kg dose, CR6261 protected against lethality from both viruses, while CR9114 provided complete protection against A/AA and protected 7 of 8 mice from Sw06 lethality. Taken together, our studies demonstrate that CR6261 and CR9114 are effective and protect mice from severe H2 influenza infection.

Scientific Focus Area: Virology

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