An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody protects mice from morbidity without interfering with the development of protective immunity to subsequent homologous challenge

Virology. 2017 Nov:511:214-221. doi: 10.1016/j.virol.2017.08.016. Epub 2017 Sep 6.

Abstract

The emergence of A(H7N9) virus strains with resistance to neuraminidase (NA) inhibitors highlights a critical need to discover new countermeasures for treatment of A(H7N9) virus-infected patients. We previously described an anti-NA mAb (3c10-3) that has prophylactic and therapeutic efficacy in mice lethally challenged with A(H7N9) virus when delivered intraperitoneally (i.p.). Here we show that intrananasal (i.n.) administration of 3c10-3 protects 100% of mice from mortality when treated 24h post-challenge and further characterize the protective efficacy of 3c10-3 using a nonlethal A(H7N9) challenge model. Administration of 3c10-3 i.p. 24h prior to challenge resulted in a significant decrease in viral lung titers and deep sequencing analysis indicated that treatment did not consistently select for viral variants in NA. Furthermore, prophylactic administration of 3c10-3 did not inhibit the development of protective immunity to subsequent homologous virus re-challenge. Taken together, 3c10-3 highlights the potential use of anti-NA mAb to mitigate influenza virus infection.

Keywords: A(H7N9); Antiviral; Avian influenza; Immunotherapeutic; Influenza; Monoclonal antibody; Neuraminidase; Passive transfer.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / immunology*
  • Disease Models, Animal
  • Immunologic Factors / administration & dosage*
  • Influenza A Virus, H7N9 Subtype / immunology*
  • Influenza A Virus, H7N9 Subtype / pathogenicity
  • Lung / virology
  • Mice
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / immunology*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / therapy*
  • Orthomyxoviridae Infections / virology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Immunologic Factors
  • Neuraminidase