Table 2.

Potential adaptive mechanisms of protection/correlates of immunity

Correlate of Protection	Description	Prevent Infection?	Vaccine Characteristics
Neutralizing antibody (viral or bacterial, adhesion factors, toxins)	IgG, matching field strains or outbreak strains	Yes, potentially	MLV or inactivated, toxoids, nonreplicating viruses and particles
Nonneutralizing antibody (virus)	IgG, potentially interfering	Questionable	MLV or inactivated, any formulation
Nonneutralizing antibody (bacteria)	IgM or IgG, somatic antigens, opsonizing and complement-mediated clearance	Yes	Bacterins or attenuated vaccines
Mucosal surface protection	IgA, viral or bacterial, adhesion factors, toxins	Yes, if infection occurs at mucosal surface, may limit infection and shedding	Attenuated vaccines, especially in intranasal or oral
Virus-specific, cytotoxic T cells	CD8+ T cells, MHC-restricted killing of infected cells	Yes, limit infection spread and pathology by destruction of infected cells	Primarily attenuated vaccines, but newer formulations with novel adjuvants
T-helper cells	CD4+ T cells	Help differentiate antibody- and cell-mediated responses, essential for memory	Attenuated and inactivated formulations with appropriate adjuvants

Data from Rimmelzwaan GF, McElhaney JE. Correlates of protection: novel generations of influenza vaccines. Vaccine 2008;26 Suppl 4:D41–4.