Vaccines to combat infectious diseases

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

Andreas Handel

2024-11-06

Question

What is the main mechanism by which a vaccine protects from infection:

  1. It induces a protective metabolic state
  2. It induces a protective immune response
  3. It induces a protective disease avoidance state
  4. All of A) - C)
  5. 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 \(\rightarrow\) Infected \(\rightarrow\) Symptomatic (often) \(\rightarrow\) Recovered and Immune (good!) or dead (bad!)

The idea behind vaccines

Infection

Healthy \(\rightarrow\) Infected \(\rightarrow\) Symptomatic (often) \(\rightarrow\) Recovered and Immune (good!) or dead (bad!)

Vaccination

Healthy \(\rightarrow\) Get Vaccine \(\rightarrow\) Symptomatic (sometimes) \(\rightarrow\) 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.

xkcd.com

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.

Polack et al 2020 NEJM

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.

xkcd.com

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