Smallpox Vaccine Shown To Provide Protective Immunity Decades After Vaccination

By Deborah Chang

In May and June of 2003, prairie dogs headed for pet stores in Wisconsin were housed in the same cage as an African rat infected with the monkeypox virus. The prairie dogs contracted the virus and went on to infect prairie dog distributors, pet store staff, the eventual owners of the infected animals, as well as veterinary clinic staff who treated the infected animals.

It caused the only known human outbreak of monkeypox in the Western Hemisphere.

Monkeypox, in the orthopoxvirus family, is one of smallpox's closest relatives, and the smallpox vaccine is similarly effective against both diseases. Researchers at the Vaccine and Gene Therapy Institute at Oregon Health & Science University (OHSU) previously had found that individuals retain smallpox antibodies for decades after receiving the vaccine, but they did not know the extent to which vaccinated individuals remained protected. That is, are those antibodies protective enough to prevent sickness after re-exposure to the virus?

The Wisconsin monkeypox outbreak proved to be an ideal opportunity for the OHSU researchers to determine the answer, and their results were published in September in Nature Medicine.

Back in 2003, representatives from the Centers for Disease Control were dispatched a week after the first patient became sick. They used a series of investigative techniques to look for the monkeypox virus in the blood or scabs of people who were in physical contact with the infected animals. The CDC reported 72 potential cases.

OHSU researchers arrived on the scene two months after the last infection was reported. "We went to Wisconsin and drew blood samples from people who contracted monkeypox and also from people who were exposed but were never sick. We had to figure out who had gotten sick and who hadn't, who was protected and who wasn't. In order to really do this, we needed better diagnostics," says Mark Slifka, assistant professor of molecular microbiology and immunology at OHSU.

The CDC could only confirm a case if they found the virus directly. The OHSU scientists looked at the patients' immune responses instead. "We were able to confirm some of the cases that the CDC found, but couldn't confirm by their techniques," says Slifka. Examining an immune response can be superior to detecting the virus directly because after the infection has cleared, the virus is no longer found in the patient's blood; however, the virus-specific immune response will be maintained long afterwards.

Slifka and his team devised a diagnostics platform consisting of three tests. The first test was a measure of the orthopoxvirus-specific antibodies that remain in an infected person's blood. Immediately after infection, the body produces antibodies to fight the invading viruses. After the infection has cleared, the level of antibodies decreases until a certain point at which the level plateaus.

By measuring the level of antibodies shortly after infection and again several months later, the difference in antibody levels can give information about whether the antibodies are present due to a childhood vaccination or due to a recent poxvirus infection. However, this test has limited usefulness if the first measurement is not taken soon after the infection has cleared.

The second test counts the number of orthopoxvirus-specific T-cells, the white blood cells that the body produces to fight invading pox viruses. A high number indicates a recent infection.

The third test is specific enough to distinguish between the monkeypox virus and the virus used in smallpox vaccinations, called vaccinia. The monkeypox genome has a protein that is not found in vaccinia. Therefore, only people who have been infected with monkeypox should have an immune response to that specific protein, regardless of vaccination status. This third method is minimally invasive and quite rapid, making it ideal for use in the field.

The OHSU researchers found that they were able to tell whether a person had been infected with greater than 90 percent certainty. Moreover, the last test is not time sensitive, allowing for accurate information to be gathered no matter how long ago the infection occurred.

The OHSU researchers successfully diagnosed reviously reported monkeypox cases confirmed by the CDC immediately post-outbreak, confirmed several cases that the CDC suspected but could not confirm, and also confirmed three more cases that had gone undetected by the CDC due to the lack of any outward symptoms. These three subjects had been vaccinated decades earlier against smallpox--evidence suggesting that the smallpox vaccine may provide protective immunity for many years.

Deborah Chang is currently pursuing a Ph.D. in physical chemistry at the University of Washington.