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When does humoral memory enhance infection?

Ariel Nikas1, Hasan Ahmed2, Mia R Moore3

  • 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.

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|August 21, 2023
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Summary
This summary is machine-generated.

Humoral memory can paradoxically enhance infection (EI-HM) through antibody-dependent enhancement or by crowding out a better immune response. Complexity in models reveals conditions where this counterintuitive effect occurs, aiding interpretation of experimental data.

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Area of Science:

  • Immunology
  • Computational Biology
  • Infectious Disease

Background:

  • Humoral memory is crucial for adaptive immunity.
  • Baseline humoral memory can sometimes increase infection load, termed enhancement of infection by humoral memory (EI-HM).

Purpose of the Study:

  • To computationally model mechanisms by which existing humoral memory can enhance infection.
  • To investigate conditions leading to EI-HM, including antibody-dependent enhancement (ADE) and immune response interference.

Main Methods:

  • Development and analysis of computational models for humoral memory and infection dynamics.
  • Modeling antibody-dependent enhancement (ADE) with varying antibody levels.
  • Simulating scenarios of cross-reactive memory responses interfering with de novo immune responses.

Main Results:

  • Simple ADE models do not inherently produce EI-HM.
  • EI-HM can occur in ADE models with less neutralizing cross-reactive antibodies or strong non-antibody immunity.
  • EI-HM can arise from cross-reactive memory 'crowding out' de novo responses, but non-antibody immunity mitigates this.
  • Model complexity can lead to qualitatively different outcomes compared to simpler models.

Conclusions:

  • Humoral memory can enhance infection through ADE or immune response interference under specific conditions.
  • Computational modeling highlights the importance of model complexity in understanding immune responses.
  • Findings may help reconcile experimental data and inform vaccine development, particularly for diseases like dengue.