TABLE 2.
Outcome of antibody protection experiments is dependent on multiple independent variables
| Variable | Parameter | Problem/example |
|---|---|---|
| Antibody | Amount | |
| Too little | Insufficient amounts of antibody in immune serum can translate into lack of protective efficacy; studies show that a defined amount of antibody is necessary for protection against C. neoformans (9) and L.nocytogenes (11) | |
| Too much | Administration of large amount of specific antibody can produce a prozone-like effect whereby more antibody is less protective than less antibody; this phenomenon has been described for polyclonal antibody preparations for S. pneumoniae and C. neoformans (43, 44). For C. neoformans, the mechanism may reflect interference with host killing mechanisms and/or alterations in cytokine response | |
| Affinity/avidity | Higher-affinity antibodies can be more effective against certain pathogens; however, the relationship between affinity and protective efficacy is poorly understood for most pathogens; for E. chaffensis, higher affinity correlated with protective efficacy (26); for S. pneumonia avidity is an important parameter of antibody efficacy (46). | |
| Specificity | Reactivity with targeted antigen is a necessary but insufficient criterion for a protective antibody; two IgM antibodies with specificity for capsular glucuronoxylomannan differ in fine specificity with one being protective and the other nonprotective (31) | |
| Isotype | Effector function of antibodies can depend on isotype; the efficacy of passive antibody for C. neoformans and E. chaffensis is highly dependent on antibody isotype (26, 49) | |
| Idiotype | Protective human antibodies to encapsulated pathogens employ certain variable region genes (reviewed in reference 39) | |
| Preparation | Immune serum is a polyclonal preparation that includes antibodies to multiple specificities and isotypes; consequently, polyclonal sera may contain blocking antibodies (21) and antibodies to other specificities that can affect the of infection; monoclonal antibodies represent one specificity and one isotype | |
| Host | Genetic background | Passive antibody efficacy depends on mouse strain for L. pneumophila (13) and C. neoformans (10) |
| Immune competency | For some pathogens, passive antibody efficacy requires a competent cell-mediated immune system (48) | |
| Model | Timing | Demonstrating the efficacy of passive antibody is easier if antibody is given before or shortly after experimental infection (7) |
| Route of infection | Efficacy of passive antibody can vary depending on the route of infection (5) | |
| Efficacy | Usual parameters of antibody efficacy are survival and reduction in organ burden, but these do not necessarily respond in parallel; for C. neoformans (16) and M. tuberculosis (45), administration of antibody prolongs survival without reducing organ colony counts | |
| Microbe | Genetic background | Some strains are more susceptible to antibody than others; an antibody to C. neoformans demonstrated highly variable efficacy against genetically different strains despite reactivity with the polysaccharide capsule (33) |
| Inoculum | Magnitude of the infecting inoculum is a critical variable in antibody protection studies (7, 44) |