Correlates of Protection

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
• 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

	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 of serum antibodies	Disease (pneumonia, otitis media, nasopharynx carriage) is prevented by >10 times higher serum antibodies