「Correlates of Protection」の版間の差分

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|+Comparison between Cases and Non-cases
 
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!Pre-exposure PRN &le;120<br>(GMT)
 
!Pre-exposure PRN &le;120<br>(GMT)
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!Post-exposure PRN >120<br>(GMT)
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!Pre-exposure PRN >120<br>(GMT)
 
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!Cases
 
!Cases
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|71 non-cases<br>(1157)
 
|71 non-cases<br>(1157)
 
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*PRN = Plaque Reduction Neutralization
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::<nowiki>*</nowiki>PRN = Plaque Reduction Neutralization
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::''t'' test ''p''<0.001
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|+Comparison among Non-cases
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!Pre-exposure PRN 216-874
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!Pre-exposure PRN &ge;1052
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!Post-exposure PRN boosted<br>suggesting subclinical infection
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|7 non-cases
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|4 non-cases
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!Post-exposure PRN unchanged
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|0 non-case
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|7 non-cases
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::Fisher's exact test ''p''<0.001

2022年10月22日 (土) 15:51時点における版

Correlates of Protection

Definitions of terms
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
  • 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)

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
Comparison between Cases and Non-cases
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
Comparison among Non-cases
Pre-exposure PRN 216-874 Pre-exposure PRN ≥1052
Post-exposure PRN boosted
suggesting subclinical infection 		7 non-cases 4 non-cases
Post-exposure PRN unchanged 0 non-case 7 non-cases
Fisher's exact test p<0.001
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