Vaccines, Blood & Biologics

ACAM2000 (Smallpox Vaccine) Questions and Answers

FDA licensed Smallpox (Vaccinia) Vaccine, Live, with the proprietary name ACAM2000, for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection. The vaccine is manufactured by Sanofi Pastuer Biologics Co. The approval and availability of this second-generation smallpox vaccine in the Strategic National Stockpile (SNS) enhances the emergency preparedness of the United States against the use of smallpox as a dangerous biological weapon.



Questions about Smallpox and ACAM2000

How does ACAM2000 work?

The vaccine is made from a virus called vaccinia, which is a "pox"-type virus related to smallpox but causes milder disease. ACAM2000 cannot cause smallpox; it does not contain the smallpox virus, but rather the "live" vaccinia virus - not dead virus like many other vaccines. For this reason, attentively caring for the vaccination site is important to prevent the virus from spreading from the vaccination site to other parts of the body, or to other people.

ACAM2000 is administered differently than the typical "shot" associated with most vaccinations. A two-pronged stainless steel (or bifurcated) needle is dipped into the vaccine solution and the skin is pricked several times in the upper arm with a droplet of the vaccine. The virus begins growing at the injection site causing a localized infection or "pock" to form. A red, itchy sore spot at the site of the vaccination within 3-4 days is an indicator that the vaccination was successful; that is, there is "a take." A blister develops at the vaccination site and then dries up forming a scab that falls off in the third week, leaving a small scar. The vaccine 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 exposure to smallpox ever occurs.

What is smallpox disease?

Smallpox is a serious, highly contagious and often fatal infectious disease caused by the variola virus that emerged in human populations thousands of years ago. A person infected with smallpox develops a rash characterized as raised pocks on the face and body. A person with smallpox has infectious saliva and close contact can spread the virus. The virus could also be spread through other body fluids and contaminated clothing or bed linen.

Hasn't smallpox been eradicated?

Following a global eradication campaign, which included vaccination, the World Health Organization certified the eradication of naturally occurring smallpox disease in 1980. Until ACAM2000 was licensed, Dryvax, manufactured by Wyeth Laboratories, Inc., was the only vaccine licensed by FDA. Routine vaccination of the American public was stopped in 1972 after the disease was eradicated from the United States. However, smallpox has the potential to be deliberately used as a weapon by terrorists. A large proportion of the population has no immunity and fatality rates could be higher than 25% if smallpox were to be released as a bioterrorist weapon.

Is ACAM2000 different than Dryvax, a vaccine used in the global eradication of smallpox?

Both vaccines are derived from the New York City Board of Health strain of vaccinia, but Dryvax was grown on the skin of calves and then essentially freeze-dried for storage. It was licensed by FDA in 1931 but is no longer manufactured. ACAM2000, a "second generation" smallpox vaccine, is derived from a clone of Dryvax, purified, and produced using modern cell culture technology.

How effective is ACAM2000?

A clinical study to demonstrate ACAM2000 is non-inferior to Dryvax was conducted in each of two populations: those who had never been vaccinated for smallpox (naive) and those who had previous vaccination. For the naive population, the percentage of scar formation at the vaccination skin site or "take rates" were similar to Dryvax vaccinees. For those previously vaccinated, the immune response generated was acceptable for ACAM2000.

Specifically, the clinical study was a multi-center, randomized, controlled study, comparing ACAM2000 to Dryvax. To compare the efficacy in persons who had never been previously vaccinated against smallpox (naive), 780 subjects received ACAM2000 and 257 subjects received Dryvax. The recipients included males and females between the ages of 18 and 30 years. In a study of people previously vaccinated against smallpox, 1,242 subjects received ACAM2000 and 405 subjects, including males and females from 31-84 years old, received Dryvax. The percentage of unvaccinated persons who developed a successful immunization reaction was similar to that of Dryvax. ACAM2000 also was found to be acceptable as a booster in those previously vaccinated for smallpox.

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Questions about Adverse Side Effects and Who Should Not be Immunized

Are there any possible side effects associated with the use of ACAM2000?
Yes, health complications can occur after receiving the vaccine, and the risk of experiencing serious side effects must be weighed against the risk of experiencing a potentially fatal smallpox infection.

The vaccine may cause myocarditis and pericarditis, which are inflammation and swelling of the heart and surrounding tissues and can be very serious. Based on clinical studies, myocarditis and/or pericarditis occur in 1 in 175 adults who get the vaccine for the first time.

In the ACAM2000 clinical trial experience, seven individuals of the 2,983 ACAM2000 first-time recipients and three individuals of the 868 Dryvax first-time recipients were suspected to have myocarditis/pericarditis. There were no cases in those subjects who had been vaccinated previously.

Serious health problems, including those that are life-threatening, can also occur in unvaccinated people who are accidentally infected by someone who has recently received the vaccine. In particular, unvaccinated people who are pregnant, or have problems with their heart or immune system, or have skin problems like eczema, dermatitis, psoriasis, and have close contact with a vaccine recipient are at an increased risk for serious problems if they become infected with the vaccine virus, either by being vaccinated, or by being in close contact with a person who was vaccinated. It is very important for the ACAM2000 recipient to properly care for the vaccination site to prevent the virus in the vaccine from spreading and infecting another part of the body and other people.

These types of serious adverse events are similar to those that occurred in the past with other smallpox vaccines.

More commonly observed side effects include: itching, sore arm, fever, headache, body ache, mild rash and fatigue.

Who should not be immunized with ACAM2000?

A healthcare provider may decide not to give ACAM2000 if a person has a weakened immune system (e.g., leukemia, HIV, AIDS, transplant recipients, people with cancer that has spread, and those undergoing treatment with medicines that suppress the immune system such as steroids, prednisone, and cancer drugs). In addition, healthcare providers may decide not to vaccinate individuals with skin conditions such as eczema, dermatitis or psoriasis who are at increased risk of complications.

How will ACAM2000 recipients be informed of its potential risks?

Every person who receives the vaccine is required to receive a Medication Guide approved by FDA (21 CFR Part 208). Medication Guides are printed handouts that are specific to particular medical products, and contain FDA-approved information that can help patients avoid serious adverse events. FDA requires that Medication Guides be issued when the Agency determines that:

  • certain information is necessary to prevent serious adverse events
  • patient decision-making should be informed by information about a known serious side effect with a product, or
  • patient adherence to directions for the use of a product are essential to its effectiveness.

ACAM2000 is the first vaccine licensed with a Medication Guide. FDA has determined that a Medication Guide is necessary for safe and effective use of the product because it could help prevent serious adverse events and inform the recipient of serious risks relative to benefit that could affect their decisions to be vaccinated.

Will ACAM2000 be available to anyone who wants it?

No, the manufacturer has stated that the vaccine won't be available to the public commercially, meaning it can't be obtained from a doctor's office. It has been purchased by the federal government for inclusion within the country's Strategic National Stockpile, for distribution by the Department of Health and Human Services, in case it is ever needed.

Currently, designated U.S. military personnel receive the vaccine. In addition, laboratory researchers working on certain pox viruses are also be eligible to receive the vaccine.

The vaccine is not recommended for use by the general population, as there is no smallpox disease in the world.

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Contact FDA

(800) 835-4709
(301) 827-1800
Consumer Affairs Branch (CBER)

Division of Communication and Consumer Affairs

Office of Communication, Outreach and Development

Food and Drug Administration

1401 Rockville Pike

Suite 200N/HFM-47

Rockville, MD 20852-1448

Page Last Updated: 08/12/2013
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