Table 1.

Approaches to partially validating correlates of protective immunity.

Approach	Shortcoming
Animal models	Relevance to humans uncertain
Human studies
Tuberculosis	More relevant to susceptibility than protection; findings may be secondary to disease and/or be nonspecific
Household contacts	Difficult to definitively characterize protected populations
Immunogenetics	More relevant to disease susceptibility; need to identify common rather than rare genetic traits
Trials of immunotherapy	Augmentation of immunity to clear bacteria from sputum may not equate to protection against tuberculosis
Modulation in a phase I/II trial (e.g., BCG)	BCG vaccination is not uniformly effective; data may not be relevant to other types of vaccines