Modeling to support influenza vaccine development
Slides: https://www.andreashandel.com/presentations/
2025-02-18
Acknowledgements
- Zane Billings, Savannah Hammerton, other group members
- Collaborators, especially Ted Ross
- NIH
Overview
Part 1: Vaccine response quantification
Part 2: Correlates of protection for animals
Part 1: Vaccine response quantification
Motivation
- We need to be able to evaluate and compare existing and new influenza vaccines.
- Immunogenicity is often a good correlate for protection. For flu specifically, HA antibodies.
- To assess broad protection, we need to quantify antibody responses to a panel of flu strains.
Quantifying vaccine responses
Quantifying vaccine responses
Quantifying vaccine responses
Comparing vaccine responses
A new method to quantify/compare vaccine responses
- Organize strains by antigenic distance
- Fit a model to more robustly estimate magnitude/breadth/strength
Strain distance
Quantifying vaccine responses
Comparing vaccine responses
Testing our method
We sampled from the panel of heterologous strains from UGAFluVac to mimic different labs
Testing our method - the results
Part 1 Summary & Discussion
- Our proposed new method seems to be more robust and suitable to quantify and compare vaccine responses.
- We would like to compare the method across actual separate studies.
- Include ‘future’ strains into analysis.
- Compare different distance measures.
- Explore models beyond linear.
Part 2: Correlates of protection for animals
Motivation
- Pre-clinical/animal studies are an important part of the vaccine development pathway.
- Results in animals inform choices for subsequent human studies.
- We need to be able to properly assess influenza vaccine efficacy in animals.
Motivation
- For both humans and animals, vaccine protection from infection/disease is the gold standard.
- Immunogenicity is often a good correlate of protection (CoP). For flu specifically, HA antibodies.
- CoP in humans are only somewhat understood. They are even less studied in animals.
CoP in adults
Hobson et al.: https://pmc.ncbi.nlm.nih.gov/articles/PMC2130285/
CoP in children
Ng et al.: https://pubmed.ncbi.nlm.nih.gov/23908481/
CoP meta-analysis
Coudeville et al.: https://pubmed.ncbi.nlm.nih.gov/20210985/
CoP in animals
- What’s the relation between antibody titers and outcomes?
- Does a 1:40 titer correspond to 50% protection in mice, ferrets, guinea pigs, etc.?
CoP in mice
Jacobsen et al.: https://pubmed.ncbi.nlm.nih.gov/28928215/
CoP in ferrets
Wong et al.: https://pubmed.ncbi.nlm.nih.gov/28303960/
Part 2 Summary & Discussion
- Not much known about CoP in animals.
- We could model the mapping from CoP to outcomes with the right kind of data:
- CoP data: antibody (and/or other immunological) measurements in non-naive animals prior to challenge
- Outcome data: Infection, weight loss, symptoms, viral load, etc.
- Broader: Relation between CoP in animals to CoP in humans?
Modeling to support influenza vaccine development Slides: https://www.andreashandel.com/presentations/ Andreas Handel 2025-02-18