Table 1.
Methods to measure antibody correlates of protection (Adapted from Plotkin, 2008)
| Vaccine (Pathogen) | Test | Correlate of Protection |
|---|---|---|
| Diphtheria (C.diphtheriae) | Toxin neutralization | 0.01–0.1 IU/ml |
| Hepatitis A | ELISA | 10 mlU/ml |
| Hepatitis B | ELISA | 10 mlU/ml |
| Hib polysaccharide (Hib) | ELISA | 1 µg/ml |
| Hib conjugate (Hib) | ELISA | 0.15 µg/ml |
| Influenza | HAI | 1/40 dilution |
| Lyme disease | ELISA | 1,100 EIA U/ml |
| Measles | Microneutralization | 120 mlU/ml |
| Pneumococcus (S.pneumoniae) |
ELISA; opsonophagocytosis | 0.2–0.35 µg/ml (for children); 1/8 dilution |
| Polio | Neutralization | 1/4 – 1/8 dilution |
| Rabies | Neutralization | 0.5 IU/ml |
| Rubella | Immunoprecipitation | 10–15 mlU/ml |
| Tetanus | Toxin neutralization | 0.1IU/ml |
| Chickenpox (VZV) | FAMA; gpELISA | ≥ 1/64 dilution; ≥ 5IU/ml |
Historically, correlates of protection have relied on the measurement of the magnitude of the antigen-specific antibody response stimulated by vaccination. Such measurements typically include the concentration of the binding antibody titers (ELISA), or some measure of the activity of the antibody, such neutralization titers or opsonophagocytic titers. When a given threshold of such a measurement is achieved or exceeded, vaccination is assumed to have reached a signature of protective immunization. These tests have become well standardized and relatively straight forward to perform. The name of the pathogen is included in parenthesis, where it’s name is different from the commonly used name for the vaccine.
Abbreviations: C. diphtheria, Corynebacterium diphtheriae; Hib, Haemophilus influenza type B; S.pneumoniae, Streptococcus pneumonia; HAI, hemagglutination inhibition; EIA, enzyme immunoassay; FAMA, fluorescent antibody to membrane antigens; gpELISA, glycoprotein antibody ELISA; VZV, varicella zoster virus.