A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis

PLoS One. 2021 Sep 1;16(9):e0256779. doi: 10.1371/journal.pone.0256779. eCollection 2021.

Abstract

Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • Disease Models, Animal
  • Drug Combinations
  • Epitope Mapping
  • Humans
  • India
  • Mesocricetus
  • Mice
  • Peptide Library
  • Post-Exposure Prophylaxis / methods*
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies virus / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Drug Combinations
  • Peptide Library

Grants and funding

Celltrion, INC provided support in the form of salaries for Pankyeom Kim, Jung Sun Ahn, CheolMin Kim, Ji Min Seo, Sun Ju Keum, Hyun Joo Lee, Min Joo Choo, Min Soo Kim, Jun Young Lee, Ki Eun Maeng, Ji Young Shin, Kye Sook Yi, and Soo Young Lee. LYSSA LLC provided support in the form of a salary for Charles E. Rupprecht. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.