Human vaccinia virus immune globulin

Uses

Human vaccinia virus immune globulin is a purified gamma globulin used to treat vaccinia infections where skin is compromised, or infections of the eyes, mouth, or other areas where vaccinia infections present a special hazard.

CNJ-016 Vaccinia Immune Globulin Intravenous Human (VIGIV) is indicated for the treatment and/or modification of: (a) eczema vaccinatum, (b) progressive vaccinia, (c) severe generalized vaccinia, (d) vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or in individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions, or (e) aberrant infections induced by vaccinia virus that include its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard .

Human vaccinia virus immune globulin is also used to associated treatment for these conditions: Eczema Vaccinatum, Generalized vaccinia

How Human vaccinia virus immune globulin works

Intravenous human vaccinia virus immune globulin (VIGIV) provides passive immunity for individuals with complications to vaccinia virus vaccination. The exact mechanism of action, however, is not yet formally known .

Nevertheless, VIGIV is ultimately an isotonic sterile solution obtained by plasmaphoresis of individuals who were vaccinated prior with vaccinia virus and possess high anti-VACV antibody titers . The potency and effect of VIGIV is described by its ability to neutralize mature virus (MV, or intracellular mature virus, IMV) . Regardless, during an infection, various forms of infectious virions are generated . In particular, the MV is a more stable form of the virus and is considered to be the form that is transmitted from host-to-host . The other important form of the infectious virus is called the extracellular virus (EV, or extracellular enveloped virus, EEV), which is critical for the spread of the virus from cell-to-cell and to distant sites within a host . EV is subsequently an important element in pathogenesis . The major target of EV neutralizing antibody in VIGIV is against the EV-specific B5 protein . VIGIV also contains antibodies that react with viral encoded immune evasion molecules, which could also participate in VIGIV's anti-poxvirus activity . Researchers have begun to try to identify all of the VACV targets in VIGIV . Due to the highly homologous proteins encoded by orthopoxviruses, there is a high degree of shared serologic cross-reactivity . Thus VIGIV could react with proteins from other orthopoxviruses and have similar therapeutic effects against other poxvirus infections .

Ultimately, however, the most commonly held consideration regarding how VIGIV is capable of eliciting its therapeutic effect is the notion that such 'pre-generated' antibodies from individuals who have already been previously vaccinated with vaccinia virus, when administered to other people, may protect against VACV infections in these newly administered individuals in a method that is perhaps similar to the natural passive transfer of maternal antibodies from a mother to her baby .

Toxicity

During clinical studies the most frequently reported adverse reactions included headache, nausea, rigors, and dizziness . Alternatively, although post-marketing experience has reported the following adverse reactions, the voluntary nature of their reporting means their frequency or possibility of causal relationships to use of the medication cannot be established reliably: infusion reactions (hypersensitivity including anaphylaxis, headache, diarrhea, tachycardia, fever, fatigue, dizziness, malaise, chills, flushing, urticaria or other skin reactions, wheezing or other chest discomforts, nausea, vomiting, rigors, back pain, myalgia, arthralgia, changes in blood pressure), renal reactions (acute renal dysfunction or failure, osmotic nephropathy), respiratory reactions (apnea, acute respiratory distress syndrome ARDS, TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm), cardiovascular reactions (cardiac arrest, thromboembolism, vascular collapse, hypotension), neurological reactions (coma, loss of consciousness, seizures, tremor, aseptic meningitis syndrome), integumentary reactions ( Stevens-Johnson syndrome, epidermolysis, erythema multiforme, dermatitis (e.g., bullous dermatitis)), hematologic reactions (pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs’) test), gastrointestinal reactions (hepatic dysfunction, abdominal pain), and pyrexia .

Food Interaction

Volume of Distribution

The volume of distribution was determined to be approximately 6630 mL .

Elimination Route

In a phase 1, double-blind study with 60 healthy subjects randomized to receive either 6000 U/kg or 9000 U/kg of intravenous human vaccinia virus immune globulin (VIGIV), the mean peak plasma concentration after intravenous administration of 6000 U/kg to 31 healthy subjects was 161 U/mL achieved within 2 hours . Furthermore, after remaining in circulation for a prolonged period of time, maximum plasma concentrations (Cmax) of VIGIV reached levels ranging from about 160 to 232 U/mL .

Half Life

The mean half-life was determined to be a range from approximately 26 to 30 days .

Clearance

Readily accessible information regarding the clearance of intravenous human vaccinia virus immune globulin (VIGIV) is not available.

Elimination Route

Readily accessible information regarding the route oof elimination of vaccinia virus immune globulin (VIGIV) is not available.

Innovators Monograph

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