Vaccines to combat infectious diseases
Slides: https://www.andreashandel.com/presentations/
2024-11-06
Question
What is the main mechanism by which a vaccine protects from infection:
- It induces a protective metabolic state
- It induces a protective immune response
- It induces a protective disease avoidance state
- All of A) - C)
- None of A) - C)
About me
- Professor of Epidemiology and Biostatistics in the College of Public Health at the University of Georgia.
- Modeling and analysis of infectious diseases, mainly influenza and norovirus.
- Work on better understanding the spread and control of infectious diseases.
- Teach courses on infectious diseases, data analysis/biostatistics and epidemiology.
More about me
- Originally from Germany, I moved to the US for graduate school. I have now lived in the US longer than in Germany.
- I trained as a physicist, I have never taken an epidemiology or biostatistics class in my life.
- If I don’t work, I grow, cook and eat, and mountain bike.
Vaccines are pretty good
xkcd.com
Vaccines are pretty good
Pollard et al 2021
The idea behind vaccines
Infection
Healthy → Infected → Symptomatic (often) → Recovered and Immune (good!) or dead (bad!)
The idea behind vaccines
Infection
Healthy → Infected → Symptomatic (often) → Recovered and Immune (good!) or dead (bad!)
Vaccination
Healthy → Get Vaccine → Symptomatic (sometimes) → Immune (often)
What are vaccines
Parts of the pathogen against which you want to create immunity
Sometimes other components that help induce the immune response
https://gladstone.org/news/how-do-vaccines-work - see also Fig 2 of Pollard et al.
How do vaccines work
- Induction of a protective, long-lived memory immune response
Pollard et al 2021, Figure 3
Challenges to make good vaccines
If you recover from measles, how long are you immune for?
If you get a measles vaccine, for how long are you protected?
If you recover from chlamydia, how long are you immune for?
If you get a chlamydia vaccine, for how long are you protected?
Evaluation of vaccines
How do we determine if vaccines are good?
- Safety
- Immunogenicity
- Efficacy/Effectiveness
- Cost-effectiveness
Vaccine Development
Knipe et al Science 2020
Outcomes of interest
Vaccines (partially) protect those who receive them (direct/individual effect):
- Reduction in risk of infection/symptoms/hospitalization/death.
- Reduction in strength of symptoms.
Outcomes of interest
Vaccines (partially) protect those who receive them (direct/individual effect):
- Reduction in risk of infection/symptoms/hospitalization/death.
- Reduction in strength of symptoms.
Vaccines can also protect non-vaccinated contacts (indirect effect).
- Reduction of susceptibles in the population leads to overall reduced spread (contagion effect).
- Reduction of infectiousness/transmission potential leads to reduced spread (infectiousness effect).
Indirect effect example
- Vaccine 1 reduces risk of clinical infection by 70%, reduces infectiousness by 30%.
- Vaccine 2 reduces risk of clinical infection by 30%, reduces infectiousness by 70%.
Gallagher et al, medRxiv 2020
Ways to evaluate vaccine impact
Measure it:
- Challenge studies
- Clinical trials
- Observational studies
Estimate it:
- Correlates of Protection
Measuring vaccine impact
Challenge studies
- One group receives the vaccine, the other placebo.
- Both groups are challenged with the pathogen under consideration.
- Measures vaccine efficacy (VE).
- Well-controlled, can use small(ish) sample size.
- Somewhat unrealistic (e.g., high challenge doses).
- Direct effect only.
- Sometimes not feasible/ethical.
Clinical trials
- One group receives the vaccine, the other placebo.
- Groups are followed and outcome (infection/disease/etc.) recorded.
- Measures vaccine efficacy (VE).
- Good balance between controlled and real-world setting.
- Usually needed for FDA approval.
- Only works if infections are high (not good for emerging pathogens).
- Can measure direct and indirect effects (but usually only direct).
- Expensive.
Observational studies
- Taking vaccine is up to individuals (so must be licensed).
- Cohort and case-control (e.g., test-negative) design.
- Measures vaccine effectiveness (VE).
- Most “real”, least controlled.
- Can lead to biased estimates.
- Can measure direct and indirect effects.
- Can be fairly inexpensive.
Estimating vaccine impact
xkcd.com
Correlates of protection (CoP)
- Determining an immunological quantity that correlates with protection can make vaccine assessment easier.
- Finding correlates of protection (for vaccines) is very valuable (but can be tricky).
xkcd.com
CoP - SARS-CoV-2 Example
Khoury et al 2021 Nat Med
CoP - Influenza Example
Coudeville et al 2010 BMC MRM
Summary
- Vaccines are one of the best public health tools we have
- Vaccines work by inducing protective immunity
- Vaccines can provide direct and indirect protection.
- There are different ways to measure vaccine effectiveness.
Questions?
https://phdcomics.com/
- Slides: https://www.andreashandel.com/presentations/
- Contact: https://www.andreashandel.com