「Correlates of Protection」の版間の差分
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| 97行目: | 97行目: | ||
!Pre-exposure PRN ≥1052 | !Pre-exposure PRN ≥1052 | ||
|- | |- | ||
| − | !Non-cases with ≥1 symptom | + | !Non-cases with<br>≥1 symptom‡ |
|26 non-cases<br>(720%) | |26 non-cases<br>(720%) | ||
|11 non-case | |11 non-case | ||
|- | |- | ||
| − | !Non-cases with no symptom | + | !Non-cases with<br>no symptom |
|11 non-case<br>(31%) | |11 non-case<br>(31%) | ||
|24 non-cases | |24 non-cases | ||
|} | |} | ||
| − | ::& | + | ::‡suggestive of subclinical infection |
| − | :: | + | ::χ<sup>2</sup> test ''p''<0.002 |
2022年10月22日 (土) 16:01時点における版
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) |
Pre-exposure PRN >120 (GMT) | |
|---|---|---|
| Cases | 8 cases (63) |
0 case |
| Non-cases | 1 non-case (56) |
71 non-cases (1157) |
- *PRN = Plaque Reduction Neutralization
- t test p<0.001
| Pre-exposure PRN 216-874 | Pre-exposure PRN ≥1052 | |
|---|---|---|
| Post-exposure PRN boosted† |
7 non-cases | 0 non-case |
| Post-exposure PRN unchanged |
4 non-case | 7 non-cases |
- †suggestive of subclinical infection
- Fisher's exact test p<0.001
| Pre-exposure PRN <1052 | Pre-exposure PRN ≥1052 | |
|---|---|---|
| Non-cases with ≥1 symptom‡ |
26 non-cases (720%) |
11 non-case |
| Non-cases with no symptom |
11 non-case (31%) |
24 non-cases |
- ‡suggestive of subclinical infection
- χ2 test p<0.002
