Chapter 3 Correlates of Protection

Question 1

Define correlate of protection.

Answer 1

Immune response statistically correlated with clinical protection.

Question 2

Define mechanistic correlate of protection.

Answer 2

Mechanism of the immune response responsible for protection against clinical disease.

Question 3

Define nonmechanistic correlate of protection.

Answer 3

Immune response that substitutes for the true immunologic correlate of protection, which may be unknown of difficult to measure.

Question 4

Define absolute correlate of protection.

Answer 4

Specific level or threshold of immune response highly correlated with protection.

Question 5

What are the ten (10) principles of protection?

Answer 5

1. Protection must be defined in relation to specific phenomena.
2. Mechanism of protection by vaccination may differ from the mechanism of protection by recovery from infection.
3. Large challenge doses can overcome immunity.
4. Most current vaccines protect through antibodies.
5. Correlates of protection may be relative.
6. Antibodies must be functional.
7. T-cell responses may be correlates of protection.
8. More than one factor may protect as cocorrelates.
9. Memory may be a mechanistic correlate of protection.
10. There exist convenient nonmechanistic correlates of protection.

Question 6

What are the levels of serum antibodies to protect against measles?

Answer 6

1. 120 mIU and over protects against clinical measles.
2. Between 200 and 1000 mIU may protect against infection and protects against clinical disease.
3. Above 1000 mIU protects against subclinical infection.

Question 7

What are the four (4) main mechanisms of protection conferred by vaccine against viral diseases?

Answer 7

1. Limiting viremia
2. Blocking mucosal replication
3. Blocking neuronal invasion
4. Blocking neuronal reactivation

Question 8

What are the four (4) main mechanisms of protection conferred by vaccine against bacterial diseases?

Answer 8

1. Limiting bacteremia
2. Blocking mucosal replication
3. Inhibiting toxin production and/or toxin activity
4. Promoting macrophage replication

Question 9

Name two (2) vaccines for which non-mechanistic correlates of protection can be useful.

Answer 9

1. Live attenuated vaccine against zoster
2. Live attenuated vaccines against rotavirus

Question 10

Name six (6) statistical challenges when developing correlates of protection in clinical trials.

Answer 10

1. Unmeasured counterfactual immune response in placebo recipients.
2. Optimization of sampling and data analysis methods.
3. Identification of cocorrelates.
4. Measurement of biomarkers shortly after vaccination and at serial time points before exposure/disease.
5. Correlations of protection for a given clinical endpoint may fail for a different clinical endpoint.
   6.

Question 11

What is the most frequent mechanistic correlate of protection?

Answer 11

Neutralizing antibodies that block the pathogen in the blood.

Question 12

What mechanism of immunity is essential for response to short incubation pathogens?

Answer 12

Effector T-cell memory response.

Question 13

What mechanism of immunity is essential for response to long incubation pathogens?

Answer 13

Central memory anamnestic response.