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Competing Heterogeneities in Vaccine Effectiveness Estimation.

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Summary
This summary is machine-generated.

Population differences in susceptibility and vaccine response affect how long vaccine protection lasts. Our models show these factors can mimic or mask true immunity waning, impacting public health strategies.

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Area of Science:

  • Immunology
  • Epidemiology
  • Mathematical Modeling

Background:

  • Waning of vaccine-induced protection is crucial for public health and immunology.
  • Population heterogeneities in susceptibility and vaccine response can alter measured vaccine effectiveness (mVE) over time, independent of pathogen evolution or true immune decay.

Approach:

  • Utilized multi-scale agent-based models, integrating epidemiological and immunological data.
  • Modeled antibody waning using a power law, linked to protection via correlates of risk and within-host viral extinction models.
  • Derived formulas quantifying heterogeneity effects, generalizing Fisher's theorem of natural selection.

Key Points:

  • Heterogeneity in pre-vaccination susceptibility accelerates apparent waning of vaccine effectiveness.
  • Heterogeneity in vaccine response decelerates apparent waning of vaccine effectiveness.
  • Underlying susceptibility heterogeneity typically dominates, but vaccine response heterogeneity can offset this effect significantly (median 29% in simulations).

Conclusions:

  • Population heterogeneities introduce biases in measured vaccine effectiveness, often appearing as faster immunity waning.
  • A subtle bias towards slower waning is also plausible due to these complex interactions.
  • The findings aid in understanding competing heterogeneities influencing vaccine-induced protection dynamics.