50 year old frozen smallpox vaccines are nearly 100 percent effective

Sep 8 2004

Diluted doses of a smallpox vaccine, originally manufactured in the 1950s and stored as a frozen preparation, are nearly 100 percent effective, allowing for expansion of the current stockpile if needed, according to an article in the September 8 issue of JAMA.

According to background information in the article, smallpox vaccination is an effective way to prevent the smallpox disease both before and after exposure to the virus. In 2002, the U.S. resumed limited vaccination, and in 2003 the military successfully inoculated more than 500,000 people. However, the current supply of the vaccine falls short of the Department of Health and Human Services goal of having one dose for every U.S. citizen, and the effectiveness of diluted doses in unclear.

Thomas R. Talbot, M.D., M.P.H., of Vanderbilt University School of Medicine, Nashville, Tenn., and colleagues injected 340 healthy volunteers with the smallpox vaccine in a double-blind, randomized controlled trial conducted between October 2002 and February 2003. Test subjects, aged 18 to 32 years, were given one of three strengths of the Aventis Pasteur smallpox vaccine (APSV): undiluted, a one to five dilution, or a one to ten dilution. The researchers followed up with the volunteers every three to five days until the injection site healed. Subjects also participated in one- and two-month evaluations and a six-month phone interview.

Of all the vaccinated individuals, 99.4 percent had successful vaccinations, defined by a vesicle or pustule at the inoculation site six to 11 days after injection. For subjects receiving an undiluted vaccine (n = 113), there was a 100 percent success rate. Those injected with the one to five dilution (n = 114) had a 98.2 percent success rate, while those receiving the one to ten dilution (n = 113) also had a 100 percent success rate of vaccination. Nearly all of the study volunteers (99.7 percent) reported at least one post vaccination symptom in the two weeks following vaccination, including vaccination site itching (96.8 percent) or pain (92.1 percent), fatigue (79.1 percent), muscle pain (78.2 percent), headache (75 percent), and fever (21.5 percent). One-fourth of the volunteers missed planned duties due to vaccine-related symptoms.

Reactogenicity (the capacity to produce adverse reactions) of the vaccine was not reduced with dilution and decreasing strengths of the vaccine. This study was conducted before reports of adverse events, including heart disease, were reported in February 2003 among civilian and military smallpox vaccine recipients. The authors report “although symptoms of cardiac disease were not actively sought from volunteers at follow-up, five volunteers reported cardiac symptoms 5 to 14 days post vaccination that resolved without [complications].”

The authors conclude: “The results of our study show that a frozen preparation of APSV has a high vaccination success rate and is an available option for smallpox vaccination of vaccinia-naïve persons, even at ten-fold diluted doses. This allows for amplification of the current smallpox vaccine stockpile [approximately 85 million doses of APSV], if needed.”

What is smallpox and what is the concern?

Smallpox is an acute, contagious, and sometimes fatal disease caused by the variola virus (an orthopoxvirus) and is marked by fever and a distinctive progressive skin rash.

What are the symptoms of smallpox?

The symptoms of smallpox begin with high fever, head and body aches, and sometimes vomiting. A rash follows that spreads and progresses to raised bumps and pus-filled blisters that crust, scab, and fall off after about three weeks, leaving a pitted scar.

How is smallpox spread?

Smallpox normally spreads from contact with infected persons. Generally, direct and fairly prolonged face-to-face contact is required to spread smallpox from one person to another. Smallpox also can be spread through direct contact with infected bodily fluids or contaminated objects such as bedding or clothing. Indirect spread is less common. In rare cases, smallpox has been spread by the virus being carried in the air in enclosed settings such as buildings, buses, and trains. Smallpox is not known to be transmitted by insects or animals.

What is the smallpox vaccine, and is it still required?

The smallpox vaccine is the only way to prevent smallpox. The vaccine is made from a virus called vaccinia, which is another "pox"-type virus related to smallpox but cannot cause smallpox. The vaccine helps the body develop immunity to smallpox. It was successfully used to eradicate smallpox from the human population. Routine vaccination of the American public against smallpox stopped in 1972 after the disease was eradicated in the United States. Until recently, the U.S. government provided the smallpox vaccine only to a few hundred scientists and medical professionals who work with smallpox and similar viruses in a research setting.

How is the vaccine given?

The smallpox vaccine is not a "shot" like many vaccinations. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. When removed, the needle retains a droplet of the vaccine. The needle is then used to prick the skin a number of times in a few seconds. The pricking is not deep, but it will cause a sore spot and one or two drops of blood to form. The vaccine is usually given in the upper arm.

How long does a smallpox vaccination last?

Past experience indicates that the first dose of the vaccine offers protection from smallpox for 3 to 5 years, with decreasing immunity thereafter. If a person is vaccinated again later, immunity lasts longer.

If someone is exposed to smallpox, is it too late to get a vaccination?

Vaccination within 3 days of exposure will completely prevent or significantly modify smallpox in the vast majority of persons. Vaccination 4 to 7 days after exposure likely offers some protection from disease or may modify the severity of disease.