Vaccines: correlates of vaccine-induced immunity.

The immune system is redundant, and B and T cells collaborate. However, almost all current vaccines work through induction of antibodies in serum or on mucosa that block infection or interfere with microbial invasion of the bloodstream. To protect, antibodies must be functional in the sense of neutralization or opsonophagocytosis. Correlates of protection after vaccination are sometimes absolute quantities but often are relative, such that most infections are prevented at a particular level of response but some will occur above that level because of a large challenge dose or deficient host factors. There may be >1 correlate of protection for a disease, which we term "cocorrelates." Either effector or central memory may correlate with protection. Cell-mediated immunity also may operate as a correlate or cocorrelate of protection against disease, rather than against infection. In situations where the true correlate of protection is unknown or difficult to measure, surrogate tests (usually antibody measurements) must suffice as predictors of protection by vaccines. Examples of each circumstance are given.