Dec 5, 2002 (CIDRAP News) As the likelihood of a large-scale smallpox vaccination program grows, the Centers for Disease Control and Prevention (CDC) is seeking to expand the government's limited supply of vaccinia immune globulin (VIG), the mainstay of treatment for severe reactions to the vaccine.
Information on the CDC's Web site says the agency has 700 doses of VIG on hand, enough to treat the reactions that would be expected if 4 million to 6 million people were vaccinated. With two companies now under contract to produce more VIG for the federal government, the CDC says it expects to have about 30,000 doses by the end of 2003.
The Bush administration is expected to announce a decision about smallpox vaccinations soon. In October, the CDC's Advisory Committee on Immunization Practices recommended vaccination for hospital workers who would be assigned to treat smallpox patients, a group that the committee estimated at roughly 510,000 nationwide. In addition, the Department of Defense reportedly has recommended vaccination for up to 500,000 military personnel who could be deployed to the Middle East in case of war with Iraq.
If the administration decided to vaccinate those groups soon, the existing supply of VIG would easily be enough, according to the CDC figures noted above. However, the supply could run short if the vaccination program were rapidly expanded to all healthcare workers and emergency personnel or to the general population.
VIG is prepared from blood plasma collected from people recently inoculated against smallpox; it contains antibody to vaccinia virus, the agent in the vaccine. The product was developed in the 1950s and found to be effective for treating eczema vaccinatum, generalized vaccinia, progressive vaccinia, and accidental implantation of vaccinia, according to the CDC. However, it was never tested in controlled studies before routine smallpox vaccination was discontinued in 1972. VIG is not recommended for post-vaccination encephalitis.
The government's current supply of VIG is in the custody of the Department of Defense, but it would be available to the CDC for civilian use if needed, CDC spokesman Curtis Allen told CIDRAP News. The existing doses were formulated in the 1990s by Baxter Healthcare, he said.
In August, Cangene Corp., based in Winnipeg, Man., announced it had signed a contract to produce up to 100,000 doses of VIG for the CDC within 5 years. Cangene has not specified a timetable for production of the drug, but the announcement said the initial CDC order was for 15,000 doses. The company said production timing will depend in large part on the supply of blood plasma used to make VIG. A Cangene official told CIDRAP News that the company is seeking 10,000 volunteers to undergo smallpox vaccination and then give blood for plasma collection. The company is working with subcontractor plasma companies to find the needed volunteers, said the official, who asked not be to named.
A second firm, DynPort Vaccine Co., Frederick, Md., is producing VIG for the Defense Department. Caroline Longanecker, a spokeswoman for DynCorp, DynPort's parent company in Reston, Va., said the DynPort product, like the existing doses, would be available to the CDC for civilian use if needed. The number of doses DynPort plans to produce was not available at this writing, but a New York Times report in November said the company had produced enough to treat 660 patients at that point.
DynPort, a joint venture of DynCorp and Porton International Inc., has a long-standing contract to supply the military with vaccines against biological weapons. Longanecker said the company is making VIG from a supply of frozen plasma from military personnel who were vaccinated against smallpox in the 1990s.
A chart supplied by the CDC shows that the agency expects to have roughly 3,000 doses of VIG by the end of this year, 24,000 doses by mid-2003, and close to 30,000 doses by the end of 2003. If the ratio of vaccinations to VIG-treatable adverse events indicated by the CDC (ie, 700 doses of VIG for 4 million to 6 million vaccines) holds up, vaccination of the entire US population would generate a need for somewhere between 33,000 and 49,000 doses of VIG. However, the CDC reports that a survey showed that in the past, VIG was used only 47 times per million first-time vaccinations, which suggests a lower need for the drug. But no one knows how many severe vaccine reactions would occur in today's population or how effectively people at risk for these complications can be screened out.
VIG is not licensed by the Food and Drug Administration and therefore could be used only under investigational new drug (IND) guidelines, which involve informed consent and follow-up monitoring. VIG produced in the past can be administered only in muscle because it contains a high proportion of aggregated protein, according to information on the CDC Web site. But the VIG being produced now is intended to be suitable for either intramuscular or intravenous administration and most likely will require a lower dose than the older product, the CDC reports.
The only alternative to VIG for treating smallpox vaccine reactions is the antiviral drug cidofovir (Vistide), according to the CDC. Licensed for the treatment of cytomegalovirus retinitis, cidofovir has shown antiviral activity against poxviruses in vitro and against cowpox and vaccinia viruses in mice, the agency says. Cidofovir can cause kidney damage, and IND rules specify that the drug can be used for vaccinia adverse reactions only when VIG is ineffective, the CDC reports.
CDC information about VIG