Correlates of Protection
目次
Correlates of Protection
| Correlates of Protection (CoP) | An immune response statistically correlated with protection |
|---|---|
| Mechanistic CoP (mCoP) | An immune response responsible for protection |
| Non-mechanistic CoP (nCoP) | An immune response surrogating mCoP and easily measured |
Identifying method of CoP (mCoP)
- Theoretically
- To measure immune responses at the time of exposure to the infection and compare them between those who get infection and not
- might be feasible by detecting immune responses of bloods donated just before an outbreak
- To measure immune responses at the time of exposure to the infection and compare them between those who get infection and not
- Practically
- To measure immune responses after the vaccination and compare them between those who get infection and not
- usually done in vaccine clinical trial phase 3
- To measure immune responses at the time of challenging exposure of vaccinated volunteers
- would be ethically approved only for milder and/or treatable infections such as seasonal influenza, cholera, dengue or cytomegalovirus
- To extrapolate vaccinated animal challenge model
- To extrapolate protective level of dosing of passive immunization (antibody treatment)
- To measure immune responses after the vaccination and compare them between those who get infection and not
Be careful
- "Immune reseponses" contain various kinds of immunological functions
- Serum antibodies with multiple isotypes and multiple functions
- Mucosal antibodies with multiple isotypes and multiple functions
- Helper T cells
- Killer T cells
- Regulatory T cells
- etc.
- Protection against infection is generally different from protection against disease
- You should focus on which type of protection you expect
| Protection against infection | Protection against disease | |
|---|---|---|
| Polio | Infection is prevented by mucosal antibodies at nasopharynx and intestine (IgA + diffused IgG) | Disease (paralysis) is prevented by serum antibodies before entering CNS via blood |
| Pneumococcus | Infection (bacteremia) is prevented by 0.20-0.35 µg/mL (ELISA) of serum antibodies | Disease (pneumonia, otitis media, nasopharynx carriage) is prevented by >10 times higher serum antibodies |
An example of measles
|
Chen, R. T., Markowitz, L. E., Albrecht, P., Stewart, J. A., Mofenson, L. M., Preblud, S. R., & Orenstein, W. A. (1990). Measles Antibody: Reevaluation of Protective Titers. In The Journal of Infectious Diseases (Vol. 162). https://doi.org/10.1093/infdis/162.5.1036
|
| Pre-exposure PRN ≤120 (GMT) |
Post-exposure PRN >120 (GMT) | |
|---|---|---|
| Cases | 8 (63) |
|
| Non-cases | 71 (1157) |
- PRN = Plaque Reduction Neutralization
