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==Correlates of Protection== | ==Correlates of Protection== | ||
{|class="wikitable | {|class="wikitable | ||
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===Be careful=== | ===Be careful=== | ||
− | *'''"Immune reseponses"''' contain various kinds of immunological functions | + | *'''"Immune reseponses"''' contain various kinds of immunological functions, thus a single immune biomarker cannot necessarily be CoP |
**Serum antibodies with multiple isotypes and multiple functions | **Serum antibodies with multiple isotypes and multiple functions | ||
**Mucosal antibodies with multiple isotypes and multiple functions | **Mucosal antibodies with multiple isotypes and multiple functions | ||
32行目: | 34行目: | ||
**Killer T cells | **Killer T cells | ||
**Regulatory T cells | **Regulatory T cells | ||
+ | **Natural killer cells | ||
+ | **Phagocytes and antigen-presenting cells | ||
**etc. | **etc. | ||
*'''Protection against infection''' is generally different from '''protection against disease''' | *'''Protection against infection''' is generally different from '''protection against disease''' | ||
48行目: | 52行目: | ||
|} | |} | ||
− | == | + | <div class="toccolours mw-collapsible mw-collapsed" style="margin-left:40px; max-width:650px; overflow:auto;"> |
− | <div style=" | + | '''An example of measles''' |
+ | <div class="mw-collapsible-content" style=""> | ||
{{Quote|content= | {{Quote|content= | ||
<div class="csl-entry">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 <i>The Journal of Infectious Diseases</i> (Vol. 162). https://doi.org/10.1093/infdis/162.5.1036</div>}} | <div class="csl-entry">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 <i>The Journal of Infectious Diseases</i> (Vol. 162). https://doi.org/10.1093/infdis/162.5.1036</div>}} | ||
− | + | ||
{|class="wikitable" style="margin-left:40px; text-align:center" | {|class="wikitable" style="margin-left:40px; text-align:center" | ||
+ | |+Comparison between Cases and Non-cases; serologically confirmed | ||
|- | |- | ||
− | ! | + | !style="width:150px"| |
− | !Pre-exposure PRN ≤120<br>(GMT) | + | !style="width:200px"|Pre-exposure PRN ≤120<br>(GMT) |
− | ! | + | !style="width:200px"|Pre-exposure PRN >120<br>(GMT) |
|- | |- | ||
!Cases | !Cases | ||
64行目: | 70行目: | ||
|- | |- | ||
!Non-cases | !Non-cases | ||
− | |1 non-case | + | |1 non-case<br>(56) |
|71 non-cases<br>(1157) | |71 non-cases<br>(1157) | ||
|} | |} | ||
− | *PRN = Plaque Reduction Neutralization | + | ::<nowiki>*</nowiki>PRN = Plaque Reduction Neutralization |
+ | ::''t'' test ''p''<0.001 | ||
+ | |||
+ | {|class="wikitable" style="margin-left:40px; text-align:center" | ||
+ | |+Comparison among serologically discarded Non-cases | ||
+ | |- | ||
+ | !style="width:150px"| | ||
+ | !style="width:200px"|Pre-exposure PRN<br>216-874 | ||
+ | !style="width:200px"|Pre-exposure PRN<br>≥1052 | ||
+ | |- | ||
+ | !Post-exposure PRN<br>boosted† | ||
+ | |7 non-cases | ||
+ | |0 non-case | ||
+ | |- | ||
+ | !Post-exposure PRN<br>unchanged | ||
+ | |4 non-cases | ||
+ | |7 non-cases | ||
+ | |} | ||
+ | ::†suggestive of subclinical infection | ||
+ | ::Fisher's exact test ''p''<0.001 | ||
+ | |||
+ | {|class="wikitable" style="margin-left:40px; text-align:center" | ||
+ | |+Comparison among serologically discarded Non-cases | ||
+ | |- | ||
+ | !style="width:150px"| | ||
+ | !style="width:200px"|Pre-exposure PRN<br><1052 | ||
+ | !style="width:200px"|Pre-exposure PRN<br>≥1052 | ||
+ | |- | ||
+ | !Non-cases with<br>≥1 symptom‡ | ||
+ | |26 non-cases | ||
+ | |11 non-cases | ||
+ | |- | ||
+ | !Non-cases with<br>no symptom | ||
+ | |11 non-cases | ||
+ | |24 non-cases | ||
+ | |} | ||
+ | ::‡suggestive of subclinical infection | ||
+ | ::χ<sup>2</sup> test ''p''<0.002 | ||
+ | |||
+ | {|class="wikitable" style="margin-left:40px; text-align:center" | ||
+ | |+Comparison between Cases and Non-cases; serologically confirmed | ||
+ | |- | ||
+ | !style="width:150px"| | ||
+ | !style="width:133px"|Pre-exposure PRN<br>≤120 | ||
+ | !style="width:133px"|Pre-exposure PRN<br>121-1051 | ||
+ | !style="width:133px"|Pre-exposure PRN<br>≥1052 | ||
+ | |- | ||
+ | !Cases with<br>no vaccine | ||
+ | |1 unvaccinated case | ||
+ | | | ||
+ | | | ||
+ | |- | ||
+ | !Cases with<br>1 vaccine | ||
+ | |7 unvaccinated case | ||
+ | | | ||
+ | | | ||
+ | |- | ||
+ | !Non-cases with<br>no vaccine | ||
+ | | | ||
+ | |0 unvaccinated non-case | ||
+ | |0 unvaccinated non-case | ||
+ | |- | ||
+ | !Non-cases with<br>1 vaccine | ||
+ | | | ||
+ | |36 vaccinated non-cases | ||
+ | |35 vaccinated non-cases | ||
+ | |} | ||
+ | </div> | ||
+ | </div> | ||
+ | |||
+ | *'''Single definitive cut-off of CoP is not commonly available''' and '''CoP is generally relative''' | ||
+ | **Generally speaking, the higher a CoP biomarker is, the more highly the subject is protected from infection or disease | ||
+ | **In other words, a certain proportion of subjects with a certain level of CoP biomarker can be protected from infection/disease | ||
+ | ***The proportion of protected subjects increases as the level of CoP biomarker rises |
2023年9月12日 (火) 10:22時点における最新版
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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, thus a single immune biomarker cannot necessarily be CoP
- 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
- Natural killer cells
- Phagocytes and antigen-presenting 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-cases | 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 | 11 non-cases |
Non-cases with no symptom |
11 non-cases | 24 non-cases |
- ‡suggestive of subclinical infection
- χ2 test p<0.002
Pre-exposure PRN ≤120 |
Pre-exposure PRN 121-1051 |
Pre-exposure PRN ≥1052 | |
---|---|---|---|
Cases with no vaccine |
1 unvaccinated case | ||
Cases with 1 vaccine |
7 unvaccinated case | ||
Non-cases with no vaccine |
0 unvaccinated non-case | 0 unvaccinated non-case | |
Non-cases with 1 vaccine |
36 vaccinated non-cases | 35 vaccinated non-cases |
- Single definitive cut-off of CoP is not commonly available and CoP is generally relative
- Generally speaking, the higher a CoP biomarker is, the more highly the subject is protected from infection or disease
- In other words, a certain proportion of subjects with a certain level of CoP biomarker can be protected from infection/disease
- The proportion of protected subjects increases as the level of CoP biomarker rises