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Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity.

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No effective treatments exist for Mayaro virus (MAYV). Researchers developed neutralizing monoclonal antibodies (mAbs), but protection in vivo required Fc effector functions, not just neutralization, for Mayaro virus control.

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Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Mayaro virus (MAYV) is an emerging alphavirus causing fever and arthritis outbreaks.
  • Currently, no specific countermeasures are available against MAYV infections.
  • Mosquito-borne alphaviruses pose a significant public health threat globally.

Purpose of the Study:

  • To generate and characterize neutralizing monoclonal antibodies (mAbs) against Mayaro virus (MAYV).
  • To investigate the mechanisms of protection conferred by these mAbs in vitro and in vivo.
  • To identify antibody features crucial for controlling MAYV infection and disease.

Main Methods:

  • Generation of 18 neutralizing monoclonal antibodies (mAbs) against Mayaro virus (MAYV).
  • In vitro assessment of antibody neutralization capacity (EC50 values) and epitope mapping.
  • In vivo efficacy studies in animal models, including Fc effector function analysis and subclass switching experiments.

Main Results:

  • Eleven of 18 generated mAbs exhibited 'elite' neutralizing activity in cell culture (EC50 <10 ng/ml).
  • Elite neutralizing mAbs targeting E1 and E2 glycoproteins showed limited efficacy in vivo.
  • The most protective mAbs demonstrated high avidity binding and potent Fc-mediated effector functions, such as phagocytosis.

Conclusions:

  • Effective control of Mayaro virus (MAYV) in vivo requires antibodies engaging Fc effector functions, beyond simple viral neutralization.
  • Murine IgG2a and humanized IgG1 antibody subclasses demonstrated superior protection against MAYV.
  • Optimal antibody-based countermeasures against MAYV and potentially other alphaviruses may necessitate a dual mechanism involving Fab-mediated neutralization and Fc effector functions.