Structural characterization of M8C10, a neutralizing antibody targeting a highly conserved prefusion-specific epitope

Xiao Xiao1,2,3, Zhiyun Wen1, Qing Chen4

  • 1Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, Pennsylvania, USA.

Journal of Virology
|November 30, 2023
PubMed
Abstract

Insights

Human metapneumovirus (hMPV) causes severe respiratory infections globally. Research into the hMPV fusion F protein is crucial for developing effective vaccines and antibody therapies against this common viral pathogen.

Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Human metapneumovirus (hMPV) is a significant global cause of lower respiratory tract infections.
  • Severe illness from hMPV disproportionately affects vulnerable groups, including infants, the elderly, and immunocompromised individuals.
  • Currently, no specific vaccines or neutralizing antibody treatments are approved for hMPV prevention or therapy.

Purpose of the Study:

  • To investigate the immune recognition of the hMPV fusion (F) protein.
  • To identify key targets for developing neutralizing antibodies against hMPV.
  • To provide insights for the creation of effective hMPV vaccines and antibody-based therapeutics.

Main Methods:

  • Analysis of antibody binding and neutralization epitopes on the hMPV F protein.
  • Characterization of the structural and functional properties of the hMPV F protein.
  • Immune response profiling against hMPV antigens.

Main Results:

  • The trimeric hMPV F protein is identified as the primary target for neutralizing antibodies found in human serum.
  • Specific epitopes on the F protein are crucial for antibody-mediated viral neutralization.
  • Detailed understanding of antibody interactions with the F protein.

Conclusions:

  • Understanding antibody recognition of the hMPV F protein is essential for therapeutic and prophylactic strategies.
  • This knowledge will guide the development of novel monoclonal antibodies and vaccines against hMPV.
  • Targeting the hMPV F protein offers a promising avenue for combating hMPV infections.