Correlates of Protection

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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
Pre-exposure PRN ≤120
(GMT)
Post-exposure PRN >120
(GMT)
Cases 8
(63)
Non-cases 71
(1157)
  • PRN = Plaque Reduction Neutralization