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Competing Heterogeneities in Vaccine Effectiveness Estimation.

Ariel Nikas1, Hasan Ahmed2, Veronika I Zarnitsyna1

  • 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Vaccines
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Summary

Population differences in susceptibility and vaccine response affect how long vaccine protection lasts. Heterogeneity in susceptibility speeds up apparent waning, while response differences slow it down, impacting measured vaccine effectiveness (mVE).

Keywords:
antibody waning by power lawfrailtyheterogeneityselectionsurvival analysisvaccine effectivenessvaccine efficacy

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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 heterogeneity in susceptibility and vaccine response can alter measured vaccine effectiveness (mVE) over time.

Purpose of the Study:

  • To investigate how population heterogeneities influence the apparent waning of vaccine effectiveness.
  • To model the impact of pre-vaccination susceptibility and vaccine response variations on mVE.

Main Methods:

  • Utilized multi-scale agent-based models parameterized with epidemiological and immunological data.
  • Incorporated antibody waning using a power law, linked to protection via correlates of risk and a within-host viral extinction model.
  • Derived formulas quantifying the effects of heterogeneity on mVE.

Main Results:

  • Heterogeneity in underlying susceptibility accelerates apparent waning of vaccine effectiveness.
  • Heterogeneity in vaccine response slows down apparent waning.
  • Underlying susceptibility heterogeneity is dominant, but vaccine response heterogeneity can offset a significant portion of this effect (median 29%).

Conclusions:

  • Population heterogeneity significantly influences the observed waning of vaccine effectiveness.
  • Apparent waning is generally biased downwards by susceptibility heterogeneity, though opposing biases are possible.
  • Understanding these heterogeneities is key for accurate interpretation of vaccine effectiveness studies.