Undesired/Unwanted Immunogenicity

This example shows a Sars-CoV-2 vaccine study where the mechanism of delivery for the study vaccine antigenic component is based off of, and enabled by the viral vector technology. In this specific use-case, the transgene encoding the full-length, membrane-bound severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is incorporated into a recombinant, replication-incompetent Human Adenovirus Type 26 (Ad26) Vector . The Sars-CoV-2 spike protein expressed by the transgene is the antigenic component of this vaccine. The "Ad26.COV2.S" study vaccine is then administered to patients. Neutralizing anti-vector antibodies (i.e. anti-Ad26 vector antibody) are closely monitored at baseline and post-study vaccine exposure visits. This is because the occurrence of the anti-vector antibodies could significantly hinder the Ad26 vector's ability to deliver the Sars-CoV-2 spike protein transgene to target cells, and consequently, either inhibits the planned vaccine therapy, or diminishes the efficacy of the study vaccine after administration.

In other words, the occurrence of the neutralizing anti-vector antibodies in response to the Ad26 vector component of the study vaccine is an "undesired and unwanted" humoral immune response, and is indicated by the ISCAT = ANTI-VECTOR ANTIBODY. In contrast, the neutralizing antibodies developed against the vaccine antigenic component Sars-CoV-2 spike protein, are "desired and wanted" humoral immune response as they are protective to the subject. These records are flagged by the ISCAT = STUDY VACCINE-RELATED IMMUNOGENICITY. The differing values in ISCAT help to make this important distinction.

For other similar examples such as vector-based gene therapies, refer to the "Rare Diseases Therapeutic Area User Guide", section 9.1, In Vivo Gene Therapy (Spinal Muscular Atrophy). Also refer to the SEND Implementation Guide v3.2, IS Example 9 for human coagulation factor IX (hFIX) transgene therapy.

The example below shows a use-case of undesired, unwanted cellular immune responses toward a protein therapeutic delivered through the viral vector technology. In this case, T-cell responses to both the viral vector and the therapeutic peptide (which is translated from the transgene delivered by the viral vector), are measured before and after study treatment. The T cell responses to both the vector and the theraptucis peptide are considered as "undesired/unwanted", which are indicated by the ISCAT = VECTOR-INDUCED IMMUNOGENICITY, and ISCAT = ANTIDRUG T CELL-MEDIATED IMMUNOGENICITY.

Additionally, both anti-drug antibodies (ADA) and anti-drug T cell-mediated immunogenicity are considered as "anti-drug immunogenicity".