Specificity neutralizing antibody assays

In summary, these are the clinically relevant questions about the immunogenicity of rDNA species-specific proteins will antibody be induced in the recipient that will neutralize the therapeutic effect or lead to immune complex disease What is the class (e.g., IgG or IgE) and specificity (i.e., reactivity against specific protein or contaminant) of the antibody induced The former antibody type could potentially neutralize the product and produce immune complex disease, while the latter could result in an anaphylaxis response. It is possible that the antibody induced is of insignificant health consequence, and its presence is known only because of improvements made in the sensitivity of detection methods with the introduction of the enzyme-linked immunosorbent (ELISA) assay. 

In vitro or in vivo biological assays (specific serum neutralization of microorganisms, specific antibody formation in animals) may be necessary, if other methods do not adequately define the active ingredient. 

Finally, it should be mentioned that for both the animal studies and the clinical studies in humans, serological assays have to be developed in advance. These tests are required for the detection of the protein drug in serum or plasma (pharmacokinetic) as well as for the detection of specific antibodies evoked by the drug. If antibodies appeared, they have to be further analyzed for neutralizing activity. This could be demonstrated by an inhibitory effect in the bioassay. 

Specific diagnosis of VEE can be accomplished by virus isolation, serologic testing, or both.110 During the first 1 to 3 days of symptoms of nonspecific febrile illness, VEE virus may be recovered from either the serum or the nasopharynx.111 Despite the theoretical possibility of person-to-person transmission of virus present in the nasopharynx, no evidence of such occurrences has been reported. Identification of the VEE subtype of an isolate involved can be accomplished by cross-neutralization tests. HI, enzyme-linked immunosorbent assay (ELISA), or plaque reduction neutralization (PRN) antibodies appear as viremia diminishes. Complement-fixing (CF) antibodies make their appearance later during convalescence. VEE IgM antibodies are present in acute phase sera,63 and it has been reported that the VEE IgM tests do not react with sera from patients with EEE or WEE.112 Since patients with encephalitis typically come to evaluation later in the course of clinical illness, virus is recovered less often from them,112 and they usually have serum antibody by the time of clinical presentation.113... 

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