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New IS domain-specific variables
Illustration of variables:
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Usage: This is a domain specific variable, and qualifies the ISTEST variable.
Description: The textual description of the entity secreted by the cells represented in the ISTEST. The combination of ISTEST and ISSCMBCL should describe "the thing, the entity or the analyte" one is measuring, without the need of additional variables.
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--BDAGNT
Binding Agent
...
Usage: This is a domain specific variable, and qualifies the ISTEST variable.
Description: The textual description of the agent that's binding to the entity in the ISTEST variable. The ISBDAGNT variable is used to indicate that there is a binding relationship between the entities in the ISTEST and ISBDAGNT variables, regardless of direction.
ISBDAGNT is not a method qualifier. It should only be used when the actual interest of the measurement is the binding interaction between the two entities in ISTEST and ISBDAGNT. In other words, the combination of ISTEST and ISBDAGNT should describe "the thing, the entity or the analyte" one is measuring, without the need of additional variables.
The binding agent may be, but not limited to, a test article, a portion of the test article, a related compound, an endogenous molecule, an allergen or an infectious agent.
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Yes. Two codelists.
-Microorgansim (MICROORG)
-Binding Agent for Immunogenicity Assessments (ISBDAGT).
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--TSTOPO
...
Test Operational Objective
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Usage: This is a domain-specific variable for LB and IS that qualifies the --TEST variable. This is a permissible variable.
Description: The textual description of the high-level purpose of the test at the operational level.
...
It is placed right after ISTSTDTL.
*When getting this ready for internal review, make sure to add TSTDTL into the IS specification table.
Yes. One codelist.
Codelist Rules: this is a non-extensible codelist and the MB SDS/CT team reserves the right to review future term request to this codelist and decide whether addition of new terms are appropriate.
Controlled Terminology:
-SCREEN: A test whose operational purpose is to determine the presence or absence of a substance or organism.
-CONFIRM: A test whose operational purpose is to verify the presence or absence of a substance or organism.
-QUANTIFY: A test whose operational purpose is to determine the amount or concentration of a substance or organism.
- use-case examples for "Quantify" are: measurements of any types of antibody titer (titration), viral load, bacterial colony count, drug toxicity concentration, etc.
- drug toxicity concentration: appears often in LOINC mapping. Also see example: https://wiki.cdisc.org/x/Qx3JB
Notes for Variable Name/Description:
Analytical purpose vs operational purpose of a test - there is a difference between the two, analytical purpose is about the analyte itself - what specific analyte are you measuring, which is why in lab we tend to have the analyte name as the LBTEST - LBTEST tells the analyte of interest. The operational purpose/objective of an analyte test is to screen, confirm then quantify the analyte - this represents a different level of purpose, and operational purpose can be applied to any analyte hence it is not analyte-specific.
Take ADA as an example, ISTEST = Binding Antidrug Antibody, this test tells you that you are looking for ADAs, not, for example, C-reactive proteins. The Screen, Confirm and Quantify then tell you the operational reason, the whys behind each performed ADA test.
REAS (Currently NSV) : it is been proposed to name this variable as REAS/Reasons Done, or at least re-use this variable. This idea is rejected because we want to control this variable with very specific values and use-cases and REAS has been used in many TAUGs with all kinds of values. We do not want to confuse people who are already using REAS.
Controlled Terminology Notes:
Is "Detection" a valid value for this codelist? We had said before that one should use "detection" when one does not know whether the test is for screening or confirmatory, however is this a synonym to screen? look at the definition for screening, how is it different from detection? Confirm is to verify the previously detected substance is present.
- Sponsor feedback is that "detected" is normally reported as a result hence this value does not belong in this codelist, because both screen and confirm are to detect the analyte, they are test qualifiers.
How about "quantify to confirm", what does that mean, is this also a valid value?
- Ine mentioned that sometimes you would perform a quantificaiton test to confirm the existence of a substance. In this instance you get a quantitative result which confirms the existence of the substance, from which you normally only report "Positive or Negative" as confirmation. However the PURPOSE of the test is still to confirm the substance, so even though in the process you are using a quantitative method, the high-level purpose is to confirm. In this instance, the correct TSTOPO value to use is still "CONFIRM". Quantitative is an attribute of the method.
Example 1: Tiered Testing of ADA
This example shows the tiered testing of antidrug antibody (ADA). Typical tiered testing scheme for ADA evaluation includes the following steps: screening, confirmatory, and "characterization". In the first tier, all evaluable samples are run in the screen assay. Samples that score positive in the screen assay are then analyzed in a confirmatory assay (tier 2). Samples that are positive for ADA in the screen and confirmatory tiers are reported as positive, while samples that are negative in either tier are reported as negative. Further tiered testing of positive samples frequently includes analysis of antibody titer and neutralizing activity. The variable "TSTOPO" has the following controlled values: SCREEN, CONFIRM and QUANTIFY to describe the operational objective or the reason behind each testing step, and also to provide uniqueness to each row of record. ISGRPID is used in this example to show that the records are related to each other, and in this case, tests are done in a tiered, sequential manner.
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| title | lb.xpt |
|---|---|
| Name | is |
...
ISBDAGNT
...
ADA_BAB
...
Binding Antidrug Antibody
...
DRUG AZ-007
...
SCREEN
...
ANTIDRUG ANTIBODIES
...
DRUG AZ-007
...
CONFIRM
...
ADA_BAB
...
Binding Antidrug Antibody
...
DRUG AZ-007
...
ANTIDRUG ANTIBODIES
...
| Domain | IS |
|---|
...
Example 2: Consolidated Reporting of ADA
The example below shows how to represent the various types of antidrug antibody tests (ADA). Of note, while most ADAs do not inhibit the pharmacodynamic activity of the drug, neutralizing antidrug antibodies (NAbs) can inhibit drug activity soon after the drug is administered. However, most ADAs, or rather, the non-NAbs can lower the drug's systemic exposure just as well by increasing the rate of drug clearance, resulting in a clinically similar outcome to that of Nabs – reduced clinical efficacy.
Rows 1-4 in this example show binding antidrug antibody reaction against the administered analogue drug, whereas rows 5-8 show cross-reactive antidrug antibody reaction against the endogenous protein that's structurally similar to the analogue study drug. Both the study drug and the endogenous protein are represented by the IS domain-specific variable "ISBDAGNT", which only qualifies the ISTEST variable. The variable, "ISTSTOPO", is also used in this dataset to describe the purpose of each testing step, and provides uniqueness to each record. ISGRPID is used to show which records are related.
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| title | lb.xpt |
|---|---|
| Name | is |
...
ISBDAGNT
...
ADA_BAB
...
Binding Antidrug Antibody
...
COAGULATION FACTOR VIII ANALOGUE DRUG
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ANTIDRUG ANTIBODIES
...
ELECTROCHEMILUMINESCENCE IMMUNOASSAY
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ADA_BAB
...
Binding Antidrug Antibody
...
COAGULATION FACTOR VIII ANALOGUE DRUG
...
ANTIDRUG ANTIBODIES
...
3
...
ADA_NAB
...
Neutralizing Binding Antidrug Antibody
...
COAGULATION FACTOR VIII ANALOGUE DRUG
...
ANTIDRUG ANTIBODIES
...
HEMAGGLUTINATION INHIBITION ASSAY
...
ADA_NAB
...
Neutralizing Binding Antidrug Antibody
...
COAGULATION FACTOR VIII ANALOGUE DRUG
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ANTIDRUG ANTIBODIES
...
HEMAGGLUTINATION INHIBITION ASSAY
...
ADA_X
...
Cross-Reactive Binding Antidrug Antibody
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ENDOGENOUS COAGULATION FACTOR VIII
...
ANTIDRUG ANTIBODIES
...
ADA_X
...
Cross-Reactive Binding Antidrug Antibody
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ENDOGENOUS COAGULATION FACTOR VIII
...
ANTIDRUG ANTIBODIES
...
ADA_NX
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Neutralizing Cross-Reactive Binding Antidrug Antibody
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ENDOGENOUS COAGULATION FACTOR VIII
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ANTIDRUG ANTIBODIES
...
HEMAGGLUTINATION INHIBITION ASSAY
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ADA_NX
...
Neutralizing Cross-Reactive Binding Antidrug Antibody
...
ENDOGENOUS COAGULATION FACTOR VIII
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ANTIDRUG ANTIBODIES
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HEMAGGLUTINATION INHIBITION ASSAY
...
| Domain | IS |
|---|
...
Example 3 - ADA Reaction Against Drug Components - Breakdown Product
This example shows the production of antidrug antibody in response to both the prodrug and its active metabolite. A prodrug is a compound that, after administration, is metabolized into a pharmacologically active drug. Please note in this example, even though only confirmatory records are reported and shown, it is assumed that the screening step has also been performed.
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| title | lb.xpt |
|---|---|
| Name | is |
...
ADA_BAB
...
Binding Antidrug Antibody
...
PRODRUG A
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ANTIDRUG ANTIBODIES
...
CONFIRM
...
ADA_BAB
...
Binding Antidrug Antibody
...
PRODRUG A
...
ANTIDRUG ANTIBODIES
...
3
...
ADA_BAB
...
Binding Antidrug Antibody
...
PRODRUG A ACTIVE METABOLITE
...
ANTIDRUG ANTIBODIES
...
CONFIRM
...
ADA_BAB
...
Binding Antidrug Antibody
...
PRODRUG A ACTIVE METABOLITE
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ANTIDRUG ANTIBODIES
...
| Domain | IS |
|---|
...
Example 4 - ADA Reaction Against Drug Components: Multiple Epitopes per Molecule
The example below shows the production of antidrug antibody in response to both the study biologic drug and also to different immunogenic epitopes of the biologic drug. This also captures an example for when the tier stops at screening (interferon beta1a assay) and goes straight into NAB from there. While unusual, it reflects the flexibility of these fields to incorporate multiple options.
A biologic drug may be biotechnology-derived therapeutic proteins (including mAbs) and peptides, some plasma-derived products (e.g., coagulation factor replacement products), and naturally derived proteins (e.g. therapeutic enzymes and toxins).
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| title | lb.xpt |
|---|---|
| Name | is |
...
ADA_BAB
...
Binding Antidrug Antibody
...
ACTIVE INTERFERON BETA 1A PORTION OF PEGINTERFERON BETA1A
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ANTIDRUG ANTIBODIES
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IMMUNOASSAY
...
2
...
ADA_BAB
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Binding Antidrug Antibody
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PEG PORTION OF PEGINTERFERON BETA1A
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ANTIDRUG ANTIBODIES
...
CONFIRM
...
ADA_BAB
...
Binding Antidrug Antibody
...
ACTIVE INTERFERON BETA 1A PORTION OF PEGINTERFERON BETA1A
...
ANTIDRUG ANTIBODIES
...
IMMUNOASSAY
...
7
...
ADA_BAB
...
Binding Antidrug Antibody
...
PEG PORTION OF PEGINTERFERON BETA1A
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ANTIDRUG ANTIBODIES
...
CONFIRM
...
| Domain | IS |
|---|
...
Example 5 - Autoimmune Disease Diagnosis
The example below shows how to represent autoantibody data.
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| title | lb.xpt |
|---|---|
| Name | is |
...
SJOGRENS SS-A60
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SJOGRENS SS-A60
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SJOGRENS SS-A52
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SJOGRENS SS-B
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| Domain | IS |
|---|
...
Example 6 - Vaccine Studies
The example below shows how to represent data about vaccine-induced immunological responses, as well immunological data collected during the trial but are not germane to the study vaccine.
| Info | ||
|---|---|---|
| ||
For vaccine studies, below are the recommended ISCAT and ISSCAT values to provide extra clarity. ISCAT and ISSCAT are not controlled therefore the below values are not mandated.
|
...
| title | lb.xpt |
|---|---|
| Name | is |
...
Rows 1-2:
...
Show the screening and quantification of "Binding Microbial-induced IgG Antibody" against the Human Respiratory Syncytial virus (RSV)-epitope B at baseline, prior to the administration of the study vaccine. The ISBDAGNT value of "HUMAN RESPIRATORY SYNCYTIAL VIRUS-EPITOPE B", is the immunogenic target in the study vaccine that could potentially stimulate the production of antibodies. Note the ISCAT value here is STUDY VACCINE-INDUCED IMMUNOGENICITY, even though at this point, study vaccine has not been administered to the subject - this is done purposefully to enable the grouping of baseline and treatment measurements.
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Rows 5-6:
...
Show the titer of "Binding Microbial-induced IgG Antibody" against the RSV-epitope B post-vaccination at visit 1 and 2. These two records show the antibody titers had increased post-vaccination, presumably due to the stimulation from the RSV study vaccine. Note the ISCAT is populated with the value "VACCINE-RELATED IMMUNOGENICITY".
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Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISBDAGNT
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ISCAT
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ISORRES
...
ISSTRESC
...
ISSTRESN
...
ISSPEC
...
ISMETHOD
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VISITNUM
...
VISIT
...
ISDTC
...
ISTSTOPO
...
RSV1230
...
IS
...
RSV1230-011
...
1
...
13668
...
Binding Microbial-induced IgG Antibody
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POSITIVE
...
POSITIVE
...
SERUM
...
ELISA
...
1
...
BASELINE
...
2017-05-27
...
SCREEN
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RSV1230
...
IS
...
RSV1230-011
...
2
...
13668
...
Binding Microbial-induced IgG Antibody
...
VACCINE-RELATED IMMUNOGENICITY
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25
...
25
...
SERUM
...
ELISA
...
1
...
BASELINE
...
2017-05-27
...
QUANTIFY
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RSV1230
...
IS
...
RSV1230-011
...
1
...
13668
...
Binding Microbial-induced IgG Antibody
...
SERUM
...
ELISA
...
1
...
BASELINE
...
2017-05-27
...
SCREEN
...
RSV1230
...
IS
...
RSV1230-011
...
2
...
13668
...
Binding Microbial-induced IgG Antibody
...
SERUM
...
ELISA
...
1
...
BASELINE
...
2017-05-27
...
QUANTIFY
...
5
...
RSV1230
...
IS
...
RSV1230-011
...
1
...
13668
...
Binding Microbial-induced IgG Antibody
...
VACCINE-RELATED IMMUNOGENICITY
...
90
...
90
...
90
...
SERUM
...
ELISA
...
2
...
VISIT 1
...
2017-07-27
...
QUANTIFY
...
RSV1230-011
...
Binding Microbial-induced IgG Antibody
...
VACCINE-RELATED IMMUNOGENICITY
...
SERUM
...
ELISA
...
QUANTIFY
...
| Domain | IS |
|---|
...
Example 7: Testing of Antibody-secreting Cells
Traditional methods such as ELISA that monitor humoral immune responses after immunization or infection typically only quantify specific antibody titers in serum. These methods do not provide any information about the actual number and location of the immune cells that secrete antibodies or cytokines.
The Enzyme-Linked ImmunoSpot (ELISpot) assay is a method to detect and quantify analyte-secreting T or B cells. Generally during Elispot testing, a colored precipitate forms and appears as spots at the sites of analyte localization (analytes typically are cytokines or antibodies), with each individual spot representing an individual analyte-secreting cell. The spots can be counted with an automated ELISpot reader system or manually, using a stereomicroscope. The example below shows how to represent the quantification of antibody-secreting cells (ASCs) as the number of spots per million peripheral blood mononuclear cells (PBMC) as determined by B-cell ELISpot from a vaccine trial.
The IS domain-specific variable, Secreted Molecule by Cells/SCMBCL, is introduced in the example below to allow flexibility in data representation and post-coordination of the various secreted antibody types and their respective ASCs. This approach liberates the ISTEST variable from having to house pre-coordinated and thus hyper-specific values crafted based on secretion and cell types.
...
| Name | is |
|---|
...
Row 1:
...
Shows the total number of IgG antibody secreting cells (ASCs) from a subject’s blood sample. In this case, ISTEST = Antibody-secreting Cells, where the entity secreted by the cells in ISTEST is represented by the variable, Secreted Molecule by Cells/ISSCMBCL.
...
Row 2:
...
Shows the number of H1 specific IgG ASCs from the same subject’s blood sample. In this case, ISTEST = Antibody-secreting Cells, where the entity secreted by the cells in ISTEST is in ISSCMBCL as "IgG antibody specific to H1 antigen".
...
Row 3:
...
Shows the number of H3 specific IgG ASCs from the same subject’s blood sample. In this case, ISTEST = Antibody-secreting Cells, where the entity secreted by the cells in ISTEST is in ISSCMBCL as "IgG antibody specific to H3 antigen".
...
Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISSCMBCL
...
ISORRES
...
ISORRESU
...
ISSTRESC
...
ISSTRESN
...
ISSTRESU
...
ISSPEC
...
ISMETHOD
...
ISDTC
...
1
...
INFL456
...
IS
...
INF02-01
...
1
...
SAMPBL0201
...
ABSCCL
...
Antibody-secreting Cells
...
VACCINE-RELATED IMMUNOGENICITY
...
2019
...
SFC/10^6 PBMC
...
2019
...
2019
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
ELISPOT
...
2011-08-08
...
2
...
INFL456
...
IS
...
INF02-01
...
2
...
SAMPBL0201
...
ABSCCL
...
Antibody-secreting Cells
...
VACCINE-RELATED IMMUNOGENICITY
...
626
...
SFC/10^6 PBMC
...
626
...
626
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
ELISPOT
...
2011-08-08
...
3
...
INFL456
...
IS
...
INF02-01
...
3
...
SAMPBL0201
...
ABSCCL
...
Antibody-secreting Cells
...
VACCINE-RELATED IMMUNOGENICITY
...
592
...
SFC/10^6 PBMC
...
592
...
592
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
ELISPOT
...
2011-08-08
Example 8: Testing of Cytokine-secreting Cells
The example below shows data from the vaccine study for Respiratory Syncytial Virus (RSV) where the subject is being vaccinated with a viral vector containing RSV Epitope B. Peripheral blood mononuclear cells are isolated from the the subject and are tested before (as baseline) and after vaccination in order to investigate whether the circulating PBMCs produce increasing amounts of Interferon gamma after re-stimulating with control or RSV-Epitope B in vitro.
The example below shows how to represent the quantification of cytokine-secreting cells as the number of spots per million peripheral blood mononuclear cells (PBMC) as determined by T-Cell ELISpot from a vaccine trial.
...
| Name | is |
|---|
...
Rows 1-2:
...
Show the measurement of Cytokine-secreting Cells (ISTEST) at baseline after stimulation with placebo (row 1) or RSV Epitope B (Row 2) respectively. The type of cytokine-secreting cells that is measured in this record produces Interferon Gamma, which is represented by the ISSCMBCL variable.
...
Rows 3-4:
...
Show the measurement of Cytokine-secreting Cells (ISTEST) at Visit 1 after stimulation with placebo (row 3) or RSV Epitope B (row 4) respectively. The type of cytokine-secreting cells that is measured in this record produces Interferon Gamma, which is represented by the ISSCMBCL variable.
...
Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISSCMBCL
...
ISORRES
...
ISORRESU
...
ISSTRESC
...
ISSTRESN
...
ISSTRESU
...
ISSPEC
...
ISMETHOD
...
ISDTC
...
1
...
RSV1230
...
IS
...
RSV1230-011
...
1
...
13668
...
CYKSCCL
...
Cytokine-secreting Cells
...
5.1
...
SFC/10^6 PBMC
...
5.1
...
5.1
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
ELISPOT
...
2017-05-27
...
2
...
RSV1230
...
IS
...
RSV1230-011
...
2
...
13668
...
CYKSCCL
...
Cytokine-secreting Cells
...
40.5
...
SFC/10^6 PBMC
...
40.5
...
40.5
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
ELISPOT
...
2017-05-27
...
3
...
RSV1230
...
IS
...
RSV1230-011
...
3
...
13668
...
CYKSCCL
...
Cytokine-secreting Cells
...
6.3
...
SFC/10^6 PBMC
...
6.3
...
6.3
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
ELISPOT
...
2017-08-27
...
SFC/10^6 PBMC
...
SFC/10^6 PBMC
...
PERIPHERAL BLOOD MONONUCLEAR CELL
...
| Domain | IS |
|---|
...
Example 9 - Microneutralization Assay
In vaccine studies, microneutralization assays are commonly used in vitro assays to quantify viral-specific neutralizing antibodies in the subject’s specimen that can block viral infection in vitro, and so provide output of vaccine efficacy.
Typically, a subject's serum and the virus of interest are added to in vitro cell cultures. If neutralizing antibodies are present in the serum, those antibodies will bind to the virus and thereby "blocking" and preventing the virus from infecting the cells in the culture plates. By vaccination with a vaccine that induces antibody response, one thus assumes that the quantity of viral-specific antibodies that are able to block viral infection are increased. The neutralization titer is the antiviral antibody titer that blocks viral infection of the cells. The NEUTRALIZING TITER 50% (also known as NT50) in the context of microneutralization assays is defined as the antiviral antibody titer that blocks 50% of viral infection of the cells. Please note that some users may also represent "Neutralizing Titer 50%" as "IC50 titer" or other test descriptors. CDISC recommends housing values such as NT50, IC50 neutralizing titer, etc. in the ISTSTDTL variable.
The example below shows data from the same Respiratory Syncytial Virus (RSV) vaccine study where the subject is being vaccinated with a viral vector containing RSV Epitope B. The subject is tested before (baseline) and after vaccination (visits 1 and 2) whether the anti-RSV binding antibodies present in the subject’s serum also have the functionality to neutralize RSV infection in vitro.
*A Neutralizing antibody is defined as antibodies that bind to, block and prevent non-self agents from infecting cells.
...
| Name | is |
|---|
...
Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISBDAGNT
...
ISORRES
...
ISORRESU
...
ISSTRESC
...
ISSTRESN
...
ISSTRESU
...
ISSPEC
...
ISMETHOD
...
ISDTC
...
1
...
RSV1230
...
IS
...
RSV1230-011
...
1
...
13668
...
Neutralizing Binding Microbial-induced Antibody
...
40
...
titer
...
40
...
40
...
titer
...
SERUM
...
MICRONEUTRALIZATION ASSAY
...
2017-05-27
...
2
...
RSV1230
...
IS
...
RSV1230-011
...
2
...
13668
...
Neutralizing Binding Microbial-induced Antibody
...
RESPIRATORY SYNCYTIAL VIRUS
...
80
...
titer
...
80
...
80
...
titer
...
SERUM
...
MICRONEUTRALIZATION ASSAY
...
2017-07-27
...
3
...
RSV1230
...
IS
...
RSV1230-011
...
3
...
13668
...
Neutralizing Binding Microbial-induced Antibody
...
RESPIRATORY SYNCYTIAL VIRUS
...
200
...
titer
...
200
...
200
...
titer
...
SERUM
...
MICRONEUTRALIZATION ASSAY
...
2017-08-27
Example 10 - Opsonophagocytic Killing Assay
In vaccine trials, the opsonophagocytic killing (OPK) assay is used as a correlate for protection to measure the "functional capacities" of vaccine-induced antibodies. This in vitro assay aids selecting promising vaccines by demonstrating whether the vaccine-induced antibodies drive efficient complement deposition and subsequent opsonophagocytic killing.
Typically this test is performed by incubating post-immunization sera of a subject with the bacterial strain of interest, phagocytes and complement proteins. If anti-bacterial antibodies are present in the subject's serum, those antibodies will bind to the bacteria together with complement proteins, this subsequently targets the bacteria for opsonization, which is the ingestion and destruction of invading non-self agents by phagocytes. By vaccination, one thus assumes that the quantity of bacterial-specific antibodies are increased, leading to a decreased number of viable bacterial cells in the presence of phagocytes, functional antibodies and complement. The assay read-out is expressed in Opsonization Index (OI) which is calculated using linear interpolation of the serum dilution containing functional antibody killing the desired percentage (usually 50%) of the bacteria, using a pre-specified algorithm.
The example below shows data from a vaccine study for Escherichia Coli (E.Coli) where the subject is being vaccinated with a vector containing E.Coli epitope X. The subject is tested before (baseline, row1) and after vaccination (rows 2-3) whether the vaccine-induced antibodies drive efficient complement deposition and subsequent opsonophagocytic killing of the E.Coli in vitro. The assay read-out is expressed in Opsonization Index (ISTSTDTL), which is a unit-less test.
A functional antibody is defined as antibodies that bind to non-self agents and initiate opsonization (destruction by complement and phagocytes) or active killing of the said non-self agent by other types of cells. Being able to recruit and activate the complement system is the key and definitive nature of a functional antibody.
...
| Name | is |
|---|
...
Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISBDAGNT
...
ISORRES
...
ISSTRESC
...
ISSTRESN
...
ISSPEC
...
ISMETHOD
...
ISDTC
...
1
...
RSV1230
...
IS
...
RSV1230-011
...
1
...
13668
...
Functional Binding Microbial-induced Antibody
...
1
...
1
...
1
...
SERUM
...
OPSONOPHAGOCYTIC KILLING ASSAY
...
2017-05-27
...
2
...
RSV1230
...
IS
...
RSV1230-011
...
2
...
13668
...
Functional Binding Microbial-induced Antibody
...
ESCHERICHIA COLI – EPITOPE X
...
3
...
3
...
3
...
SERUM
...
OPSONOPHAGOCYTIC KILLING ASSAY
...
2017-07-27
...
3
...
RSV1230
...
IS
...
RSV1230-011
...
3
...
13668
...
Functional Binding Microbial-induced Antibody
...
ESCHERICHIA COLI – EPITOPE X
...
5
...
5
...
5
...
SERUM
...
OPSONOPHAGOCYTIC KILLING ASSAY
...
2017-09-27
Example 11 - Hemagglutination Inhibition Assay
The OI data below shows how to represent the various taxanomic naming levels of Influenza A virus (A/duck/Hong Kong/33/1976(H10N1)).
https://www.cdc.gov/flu/about/viruses/types.htm
...
| Name | oi |
|---|
...
Row
...
STUDYID
...
DOMAIN
...
NHOID
...
ISSEQ
...
OIPARMCD
...
OIPARM
...
OIVAL
...
1
...
INF1230
...
OI
...
INFAHK33
...
1
...
Influenza A virus
...
3
...
INF1230
...
OI
...
INFAHK33
...
3
...
INF1230
...
OI
...
INFAHK33
...
INF1230
...
| Name | is |
|---|
...
Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISBDAGNT
...
ISORRES
...
ISORRESU
...
ISSTRESC
...
ISSTRESN
...
ISSTRESU
...
ISSPEC
...
ISMETHOD
...
ISDTC
...
1
...
INF1230
...
IS
...
INF1230-011
...
1
...
13668
...
MBAB
...
Microbial-induced Antibody
...
40
...
titer
...
40
...
40
...
titer
...
SERUM
...
HEMAGGLUTINATION INHIBITION ASSAY
...
2017-05-27
...
2
...
INF1230
...
IS
...
INF1230-011
...
2
...
13668
...
Microbial-induced Antibody
...
Influenza Hemagglutinin
...
80
...
titer
...
80
...
80
...
titer
...
SERUM
...
HEMAGGLUTINATION INHIBITION ASSAY
...
2017-07-27
...
3
...
INF1230
...
IS
...
INF1230-011
...
3
...
13668
...
MBAB
...
Microbial-induced Antibody
...
Influenza Hemagglutinin
...
200
...
titer
...
200
...
200
...
titer
...
SERUM
...
HEMAGGLUTINATION INHIBITION ASSAY
...
2017-08-27
...
Row
...
STUDYID
...
DOMAIN
...
USUBJID
...
ISSEQ
...
ISREFID
...
ISTESTCD
...
ISTEST
...
ISBDAGNT
...
ISORRES
...
ISORRESU
...
ISSTRESC
...
ISSTRESN
...
ISSTRESU
...
ISSPEC
...
ISMETHOD
...
ISDTC
...
1
...
INF1230
...
IS
...
INF1230-011
...
1
...
13668
...
MBAB
...
Microbial-induced Antibody
...
40
...
titer
...
40
...
40
...
titer
...
SERUM
...
HEMAGGLUTINATION INHIBITION ASSAY
...
2017-05-27
...
2
...
INF1230
...
IS
...
INF1230-011
...
2
...
13668
...
Microbial-induced Antibody
...
Influenza A virus (A/duck/Hong Kong/33/1976(H10N1)) Hemagglutinin
...
80
...
titer
...
80
...
80
...
titer
...
SERUM
...
HEMAGGLUTINATION INHIBITION ASSAY
...
2017-07-27
...
3
...
INF1230
...
IS
...
INF1230-011
...
3
...
13668
...
MBAB
...
Microbial-induced Antibody
...
Influenza A virus (A/duck/Hong Kong/33/1976(H10N1)) Hemagglutinin
...
200
...
titer
...
200
...
200
...
titer
...
SERUM
...
HEMAGGLUTINATION INHIBITION ASSAY
...
2017-08-27
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