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==Correlates of Protection==
{|class="wikitable
*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''
*Practically
**To measure immune responses '''after the vaccination''' and compare them between those who get infection and not
**To extrapolate vaccinated animal challenge model
**To extrapolate protective level of dosing of passive immunization (antibody treatment)
===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
{|class="wikitable" style="max-width:600px; margin-left:40px"
|-
! !!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
|}
<div class="toccolours mw-collapsible mw-collapsed" style="margin-left:40px; max-width:650px; overflow:auto;">
'''An example of measles'''
<div class="mw-collapsible-content" style="">
{{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>}}
{|class="wikitable" style="margin-left:40px; text-align:center"
|+Comparison between Cases and Non-cases; serologically confirmed
|-
!style="width:150px"|
!style="width:200px"|Pre-exposure PRN ≤120<br>(GMT)
!style="width:200px"|Pre-exposure PRN >120<br>(GMT)
|-
!Cases
|8 cases<br>(63)
|0 case
|-
!Non-cases
|1 non-case<br>(56)
|71 non-cases<br>(1157)
|}
::<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
