Analysis and Modeling to evaluate influenza vaccine responses
Slides: https://www.andreashandel.com/presentations/
2023-06-15
Acknowledgements
- Zane Billings - for doing most of the work
- Ted Ross, Andrea Sant - for data sharing
- Many other colleagues and collaborators
- NIH
Influenza heterogeneity
Factors that influence influenza vaccine responses
How do we define a vaccine response?
Pre-vaccination titer and vaccine response
Introduction
- More pre-vaccination titer leads to more post-vaccination titer, but reduced boost.
- Called response blunting, antibody ceiling effect, negative interference.
- For a nice summary, see Oidtman et al. 2021 Trends Mic
Schematic
Pre-vaccination titer and vaccine response
Left: H1N1 vaccine, Right: H5N1 vaccine. Zarnitsyna et al 2015 Phil Trans B.
Pre-vaccination titer and vaccine response
Pre-vaccination titer and vaccine response
x-axis: titer increase. Left: H1N1, Right: H3N2. Moritzky et al 2023 JID.
UoR cohort - IgG titer increase
UoR cohort - HAI titer increase
H1N1 Pre-vaccination titer and boost
H3N2 Pre-vaccination titer and boost
Epitope-masking can explain some of those patterns
Zarnitsyna et al 2015 Phil Trans B, 2016 Plos Path.
Modeling pre-vaccination titer and heterologous vaccine response
Extension of the model can be used to explore predictions for heterologous response.
free antigen (type 1)˙Hf=−k1A1Hf−k2A2Hf−dfHfbound antigen (type 1)˙Hb=k1A1Hf+k2A2Hf−dbHbB-cell type 1˙B1=s1B1Hfp1+Hfantibody type 1˙A1=g1B1−k1A1Hf−d1A1B-cell type 2˙B2=s2B2Hfp2+Hfantibody type 2˙A2=g2B2−k2A2Hf−d2A2
With k2=k1(1−AD), s2=s1(1−AD)
Modeling pre-vaccination titer and heterologous vaccine response
Extension of the model can be used to explore predictions for heterologous response for different antigenic distance (AD).
Heterologous vaccine response patterns - H1N1
Heterologous vaccine response patterns - H1N1
Heterologous vaccine response patterns - H1N1
Heterologous vaccine response patterns - H3N2
Heterologous vaccine response patterns - H3N2
Heterologous vaccine response patterns - H3N2
Epitope-masking can’t be the whole story
Pattern also seen for CD4 T-cells.
x-axis: titer increase. Left: H1N1, Right: H3N2. Moritzky et al 2023 JID.
Next steps
- More careful comparison of model and data (fitting).
- Extension of existing models to account for observed patterns in data.
- Think about other important features (e.g., OAS/imprinting) and try to account for them in models.
Conceptual Framework
Bonus Slides
The role of prior vaccinations
- There is some evidence that repeat vaccinations leads to reduced vaccine efficacy (VE).
- Is the reduced VE mediated by antibody titers?
- Repeat vaccinators mount a less strong vaccine response. But is that just because they start at a higher pre-vaccination titers?
Repeat vaccinations
No impact other than pre-vaccine antibodies?
Repeat vaccinations
x-axis: titer increase. Teal: unvaccinated, Orange: previously vaccinated. Left: H1N1, Right: H3N2. Moritzky et al 2023 JID.
UoR - IgG
UoR - HAI
Repeat vaccinations - H1N1 HAI
Repeat vaccinations - heterologous H1N1
Repeat vaccinations - heterologous H1N1
Repeat vaccinations - heterologous H1N1
Repeat vaccinations and post-vac titers
