Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding

Front Immunol. 2021 Dec 16;12:790918. doi: 10.3389/fimmu.2021.790918. eCollection 2021.

Abstract

We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of porcine mAb pb18, against the K160-163 site of the hemagglutinin, significantly reduced lung pathology and nasal virus shedding and eliminated virus from the lung of pigs following H1N1pdm09 challenge. When given at 1 mg/kg, pb18 significantly reduced lung pathology and lung and BAL virus loads, but not nasal shedding. Similarly, when pb18 was given in combination with pb27, which recognized the K130 site, at 1 mg/kg each, lung virus load and pathology were reduced, although without an apparent additive or synergistic effect. No evidence for mAb driven virus evolution was detected. These data indicate that intravenous administration of high doses was required to reduce nasal virus shedding, although this was inconsistent and seldom complete. In contrast, the effect on lung pathology and lung virus load is consistent and is also seen at a one log lower dose, strongly indicating that a lower dose might be sufficient to reduce severity of disease, but for prevention of transmission other measures would be needed.

Keywords: influenza monoclonal antibody; monoclonal antibody therapy; mucosal immunity; pandemic H1N1 virus; swine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Viral / administration & dosage*
  • Bronchoalveolar Lavage Fluid / virology
  • Disease Models, Animal
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / isolation & purification*
  • Influenza, Human / drug therapy*
  • Influenza, Human / immunology
  • Influenza, Human / transmission
  • Influenza, Human / virology
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / pathology
  • Nasal Mucosa / virology
  • Sus scrofa
  • Viral Load / immunology
  • Virus Shedding / drug effects
  • Virus Shedding / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • H1N1 virus hemagglutinin
  • Hemagglutinin Glycoproteins, Influenza Virus