The impact of seasonal influenza vaccine dose on homologous and heterologous immunity
Slides: https://www.andreashandel.com/presentations/
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.
Yij∼Normal(μij,σ)μij=αID[i]+βdoseDOSEi+βageAGEi+βpPHAIi,j+βsexSEXi+βraceRACEi
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?
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