The impact of seasonal influenza vaccine dose on homologous and heterologous immunity

Slides: https://www.andreashandel.com/presentations/

Andreas Handel

2022-09-10 12:46:16

Motivation

  • Current influenza vaccines are not that great.
  • Immunity following vaccination is especially low in older individuals.
  • An increase in dose (antigen) for the Fluzone vaccine has been shown to lead to somewhat better protection against the vaccine strains in older individuals.
  • It is unclear if the high dose (HD) vaccine leads to better protection against strains other than the vaccine strains.

Setup

  • Cohort of individuals who received Fluzone vaccine over multiple seasons.
  • Trivalent or quadrivalent standard dose (SD, 15µg) Fluzone vaccine was the default.
  • Individuals >=65 years were offered the high-dose (HD, 60µg) trivalent vaccine.
  • We evaluated immune response following vaccination, specifically antibodies as measured by hemagglutination inhibition assay (HAI).

Question: What is the impact of standard dose (SD) versus high dose (HD) vaccine on antibodies, especially against non-vaccine strains?

Study population

“Raw” data - homologous responses

“Raw” data - heterologous responses

Outcomes of interest

We investigate 4 antibody titer outcomes for each strain:

  • HAI Titer increase following vaccination
  • Post-vaccination HAI titer
  • Seroconversion, defined as pre-vaccination titer <1:10 (detection limit) and post-vaccination titer >= 1:40 OR a >=4-fold increase
  • Seroprotection, defined as post-vaccination titer >= 1:40

HAI values are converted to be between 0 - N, with limit of detection = 0, lowest dilution (1:10) = 1, up to highest dilution (1:20480) = 12.

Methods

Multilevel Bayesian mixed effects models. Mix of fixed and pooled/adaptive priors.

\(\begin{aligned} Y_{ij} & \sim \textrm{Normal}(\mu_{ij}, \sigma) \\ \mu_{ij} & = \alpha_{ID[i]} + \beta_{dose} DOSE_i \\ & + \beta_{age} AGE_i + \beta_{p} PHAI_{i,j} \\ & + \beta_{sex} SEX_i + \beta_{race} RACE_i \end{aligned}\)

Notation: i: individuals, j: strains.

Results - homologous response

Median and 89% equal-tailed credible interval

Heterologous H1N1 titer increase

Heterologous H1N1 seroconversion

Overall vaccine response - homologous

Overall vaccine response - heterologous

Research project summary

  • HD vaccine does overall provide better induction of immunity against vaccine strains.
  • HD is not always better for heterologous responses against non-vaccine strains.
  • There is noticeable variability between vaccine strains and seasons.

Some other projects

R packages to make modeling easier I

R packages to make modeling easier II

For research (in progress):

Online modeling/analysis courses

Acknowledgements

  • Collaborators:
    • Research project: Yang Ge, Amanda Skarlupta, Zane Billings, Ye Shen, Justin Bahl, Paul Thomas, Ted Ross
    • Other projects: See each website
  • Funding:
    • NIH

Questions?