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Vaccines

Dryvax (Smallpox Vaccine) Questions and Answers

What is smallpox?

Naturally occurring smallpox is a serious infectious disease that is usually spread from person to person through close contact. It is caused by the variola virus. Across studies, naturally occurring smallpox (variola major) has a fatality rate of approximately 30%. Smallpox can also cause permanent disabilities, such as terrible scarring and blindness. There is no FDA-approved treatment for smallpox disease. The only approved preventive intervention is vaccination.

The last case of smallpox in the United States (U.S.) occurred in 1949, and routine vaccination in the U.S. was stopped in1972. The last naturally occurring case in the world occurred in Somalia in 1977, and the World Health Organization determined in 1980 that the global vaccination campaign against smallpox had been successful in eliminating naturally occurring disease from the world. As a result, routine vaccination against smallpox on a worldwide basis was stopped because it was no longer necessary for prevention.

More recently, the U.S. government has become concerned that smallpox could be used as a weapon of bioterrorism, and is developing new vaccination strategies for both military personnel and civilians. Smallpox (variola major) is a particularly dangerous biological weapon threat because of the severity of the illness it causes and the fact that it can be spread from person to person.

What is Dryvax?

Smallpox Vaccine, Dried, Calf Lymph Type, trade name Dryvax, manufactured by Wyeth Laboratories, helps the body develop immunity to smallpox., Dryvax is a live-virus preparation of vaccinia virus prepared from calf lymph. The calf lymph is purified, concentrated, and dried by a process called lyophilization. Vaccinia is a "pox" type virus that is related to the virus that causes smallpox. The vaccinia virus can protect against smallpox, and unlike smallpox, vaccinia rarely causes serious disease in previously healthy people. The vaccine cannot give you smallpox.

Dryvax was first approved in 1931. The existing doses of Dryvax vaccine were manufactured in the 1970s and early 1980s and stored frozen at -20°C. Licensed vaccine lots have to meet specific criteria in order to be distributed, including current testing to demonstrate the potency (strength) of the vaccine and the container-closure integrity of the vaccine vials. In October 2002, FDA approved a new 100-dose kit for Dryvax, which includes a new supply of diluent (the liquid mixed with the dried vaccine before it is administered) and bifurcated (double pointed) needles for vaccine administration. Prior to this approval, Dryvax had been available for use only under an investigational new drug application ( IND). With this approval, Dryvax can again be distributed and used as an approved product. All supplies of Dryvax for civilian use are under the control of the Centers for Disease Control and Prevention, in conjunction with the Department of Health and Human Services.

What is the indication for Dryvax vaccine?

Dryvax smallpox vaccine is indicated for active immunization against smallpox disease. Please see the package insert (label) for more information.

What is known about the efficacy of Dryvax?

In addition to its use in the U.S., Dryvax was used in a major phase of the successful program to eliminate smallpox carried out in West and Central Africa and in other parts of the global program (Federal Register 45:25683-25688, 1980). As demonstrated during this global campaign, a vaccine "take," as evidenced by the presence of a scar resulting from previous smallpox vaccination, was associated with protection against disease. More detail on what constitutes a take is found in the following section.

What does the vaccination site look like after vaccination with Dryvax?

Please see the package insert for details of the vaccination procedure. The vaccine is administered to the superficial layers of the skin using a bifurcated, or double-pointed, needle. With the primary vaccination (first time a person is vaccinated), as the vaccine virus replicates in the vaccination site, a raised area called a papule appears at the site of vaccination about 2 to 5 days after vaccination. This type of reaction is evidence that the person has been successfully immunized, and is known as a "take." This becomes a vesicle (a blister) on the 5th or 6th day, which becomes pustular (pus-filled) and surrounded by erythema (redness) and induration (swelling). The maximal area of erythema is attained between the 8th and 12th day following vaccination (usually the 10th). The redness and swelling then subside, and a scab forms which comes off between the 14th to 21st days. Once the scab falls off, a permanent scar is left behind.

Photographs of the typical skin reaction to the smallpox vaccine can be viewed on the CDC's Smallpox Vaccine page

Vaccine virus (vaccinia) from the vaccination site can be spread to other parts of the body and to other people until the scab falls off. At the height of the reaction, there is usually regional lymphadenopathy (swollen lymph glands in the armpit) and there may be fever and malaise (a general feeling of illness). The vaccine "take" in previously immunized individuals may not be as pronounced.

What adverse reactions can occur after vaccination with Dryvax?

Fever, malaise and regional lymphadenopathy are common following vaccination. However, fever is less common in adults than in children after vaccination or revaccination. Also, a considerable injection site reaction is expected with successful vaccination. Accidental spread of the vaccine virus from the vaccination site to other parts of the body is one of the most frequent complications of vaccination. It usually results when the vaccinated individual touches the infected vaccination site and unintentionally transfers the virus to other parts of their body. Generalized vaccinia (manifested by skin lesion(s) at locations other than the vaccination site) among persons without underlying illnesses is characterized by a vesicular rash (a rash consisting of blisters) of varying size. The rash generally goes away and requires little or no therapy except among patients who have serious underlying illnesses.

The serious side effects of smallpox vaccination have been well documented, for example, in this publication: Lane JM, Ruben FL, Neff JM, Millar JD. Complication of smallpox vaccination, 1968. N Engl J Med 1969;281:1201-8. More severe complications that may follow either primary vaccination or revaccination include nervous system involvement by the vaccine such as postvaccinial encephalitis, encephalomyelitis, and encephalopathy, and more serious skin infections including progressive vaccinia (vaccinia necrosum), which usually occurs in individuals with weakened immune systems, and eczema vaccinatum, which usually occurs in people with eczema and related skin diseases (see the CDC website for photos of these complications). Such complications may result in severe disability, permanent neurological damage, and/or death. Although a rare event, approximately 1 death per million primary vaccinations and 1 death per 4 million revaccinations have occurred after smallpox vaccination. Death is most often the result of postvaccinial encephalitis or progressive vaccinia. Death has also been reported in unvaccinated individuals to whom the virus was spread by contact with vaccinated individuals.

Please see the package insert for how to minimize the risk of spreading the virus to another area of the body or to another person.

How does Dryvax work and why does it cause all these side effects?

Dryvax, contains a living virus (the vaccinia virus). Following vaccination, this living virus grows in the skin and stimulates a person's immune system to develop antibodies and cells in the blood and elsewhere that can then help the body fight off a real smallpox infection if the person is ever exposed. Most of the common side effects of the vaccine (like fever and the skin rash and weakness) occur from the growth of the vaccine virus itself or from the vaccinated person's reaction to the virus. Many of the rare, most serious side effects, occur in people whose immune systems fail to effectively fight off the virus. These types of adverse events, though unwelcome and unwanted, are due to the nature of the vaccinia virus itself and are expected to occur in a certain number of individuals (see above). The occurrence of such serious, life-threatening events is expected with use of currently available smallpox vaccines and is part of the reason that anyone receiving a smallpox vaccine, even licensed Dryvax, should be informed of the potential risks.

What are the contraindications to vaccination with Dryvax (who should not normally receive the vaccine)?

Contraindications for Non-Emergency Vaccine Use are summarized here. Please see the package insert for complete details.

Primary vaccination AND revaccination with smallpox vaccine are contraindicated:

  • For any individuals who are allergic to any component of the vaccine.
  • For infants less than12 months of age. Although children were previously routinely immunized when smallpox was a naturally occurring disease, the Advisory Committee on Immunization Practices (ACIP) currently advises against non-emergency use of smallpox vaccine in children less than 18 years of age.
  • For individuals of any age with eczema or past history of eczema or for those whose household contacts have eczema or past history of eczema.
  • For individuals of any age with other acute, chronic, or exfoliative (peeling) skin conditions (e.g., atopic dermatitis, wounds, burns, impetigo, or varicella zoster), and for siblings or other household contacts of such individuals.
  • For persons of any age receiving therapy with systemic corticosteroids (such as prednisone, hydrocortisone, dexamethasone, methylprednisolone and others; ask your physician) at certain doses or immunosuppressive drugs or radiation. Household contacts of such persons should not be vaccinated.
  • For individuals with congenital or acquired deficiencies of the immune system, including individuals infected with the human immunodeficiency virus (HIV). Household contacts of such persons should not be vaccinated.
  • For individuals with immunosuppression (e.g., leukemia, lymphomas of any type, generalized malignancy, solid organ transplantation, hematopoietic stem cell transplantation, cellular or humoral immunity disorders, agammaglobulinemia, or other malignant neoplasms affecting the bone marrow or lymphatic systems), or household contacts of such individuals.
  • During pregnancy, suspected pregnancy, or for household contacts of pregnant women.

What are the contraindications for immunization during a smallpox emergency or following possible exposure to smallpox?

There are no absolute contraindications regarding vaccination of a person with a high-risk exposure to smallpox. Persons at greatest risk of experiencing serious vaccination complications are often those at greatest risk of death from smallpox. If a relative contraindication to vaccination exists, the risk of experiencing serious vaccination complications must be weighed against the risk of experiencing a potentially fatal smallpox infection. The decision of whether a person at increased risk of complications should receive vaccine should be made by you and your health care provider based on specific knowledge of your medical situation and the potential exposure to smallpox.

Is there more information regarding the use of Dryvax?

This vaccine has been evaluated in a number of recent studies, either as the primary vaccine being studied or as a comparison vaccine. One such study was published recently (Frey SE et al. Clinical responses to undiluted and diluted smallpox vaccine. N Engl J Med 2002:346:1265-74). In this study, 680 adults who had not been previously immunized were vaccinated with undiluted Dryvax (mean titer, 10 8.1 plaque forming units per milliliter), a 1:5 dilution, or a 1:10 dilution of Dryvax with use of a bifurcated needle. Success rates for "takes" were high, and did not differ significantly among the dilution groups. Take rates ranged from 97.1 to 99.1 percent after the first vaccination. As expected, both the undiluted and diluted Dryvax vaccines caused frequent occurrence of the known side effects. In addition to the expected formation of a pus-filled blister on the skin where the vaccination was given, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue and chills. Approximately one-third of the study participants missed some work, school, recreational activities, or sleep because of adverse reactions to vaccination.

Are other smallpox vaccines in development?

The National Institute of Allergy and Infectious Diseases (NIAID) is supporting studies of other smallpox vaccines under IND. A summary of the current studies in progress can be found on the NIAID web site. Additional information about the design of these trials is also available (enter "smallpox" into the query field).

NIH is supporting the study of new generation smallpox vaccines that are made using even more attenuated, or weakened, forms of the smallpox vaccine virus. One such attenuated vaccine is referred to as modified vaccinia Ankara (MVA), a potential alternative smallpox vaccine that is under study based on the hope that it might be both safe and effective for individuals at high risk of complications from existing smallpox vaccines. A summary of the NIAID sponsored phase 1 trial of this vaccine candidate is available.

 
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