2020-12-01 15:34:43

Introduction

  • Inoculum dose is an important determinant of infection or vaccination outcomes.
  • For infection, higher dose is often associated with greater risk of infection (e.g. ID50) and more severe outcomes (e.g. LD50).
  • For vaccines, dose is thought to impact both immunogenicity and side effects (morbidity).

Current approaches to dose choice

Possible important issues

  • Impact of dose on immunogenicity might not be monotone (e.g. AstraZeneca COVID vaccine).
  • For a universal influenza vaccine breadth of protection is important.

Modeling the impact of dose

Current project - study population

  • Analysis of antibody responses of individuals who received seasonal flu vaccine.
  • Individuals were vaccinated (some repeatedly) during 2014/15 - 2018/19 flu seasons.
  • The default vaccine was the trivalent or quadrivalent standard dose (SD, 15µg) Fluzone vaccine.
  • Individuals >65 were offered the high-dose (HD, 60µg) trivalent vaccine.

Current project - analysis

  • What is the impact of standard dose (SD) versus high dose (HD) vaccine on immune outcomes?
  • Investigate 3 antibody titer (HAI) outcomes:
    • Fold change in HAI titer following vaccination.
    • Seroconversion, defined as pre-vaccination HAI titer <1:10 (LOD) and post-vaccination titer >= 1:40 OR a >=4-fold increase.
    • Seroprotection, defined as post-vaccination HAI >= 1:40.
  • Focus on individuals >=65 years.

Homologous responses, H1N1 HAI ratio

Median and 95% Credible Interval from a univariate analysis

Median and 95% Credible Interval from a univariate analysis

Homologous responses, H1N1 seroconversion fraction

Median and 95% Credible Interval from a univariate analysis

Median and 95% Credible Interval from a univariate analysis

Homologous responses, H1N1 seroprotection fraction

Median and 95% Credible Interval from a univariate analysis

Median and 95% Credible Interval from a univariate analysis

Homologous responses, H3N2 HAI ratio

Median and 95% Credible Interval from a univariate analysis

Median and 95% Credible Interval from a univariate analysis

Homologous responses, H3N2 seroconversion fraction

Median and 95% Credible Interval from a univariate analysis

Median and 95% Credible Interval from a univariate analysis

Homologous responses, H3N2 seroprotection fraction