OHSU researchers study smallpox vaccination protection over time

Scientists study those vaccinated more than 60 years ago versus one year ago

Oregon Health & Science University researchers are studying the effectiveness of the smallpox vaccine in patients who received inoculations decades ago compared with those vaccinated more recently. The universal belief has been that smallpox vaccinations provide protection for only three to five years. Until now scientists and physicians assumed that anyone vaccinated more than five years ago had little to no protection left. However, researchers at the OHSU Vaccine and Gene Therapy Institute believe that conventional thinking may not be true. To test their theories, scientists are studying how much protection the smallpox vaccination provides 67 years later versus just a year ago. This information may provide a more accurate way of estimating the spread of a potential smallpox outbreak, because nearly 95 percent of Americans older than 35 were vaccinated, and many may still have strong immunity against smallpox.

"I've been intrigued about immunological memory for more than a decade. It's exciting to be able to apply this interest to something that's relevant to our community right now," said Mark Slifka, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine "We know that people who contract yellow fever, polio, measles or mumps gain a lifelong immunity to those diseases. Now we want to see if this is universally true for other viruses, such as vaccinia, the virus used for immunizing against smallpox."

Vaccinia is a virus contained within the smallpox vaccine and is closely related to smallpox. However, in most cases, vaccinia does not cause serious health problems. The virus promotes smallpox protection by causing the body to produce protective antibodies and white blood cells that can search for and destroy smallpox-infected cells.

Slifka's lab is collecting blood samples from study participants. These samples are then analyzed to determine the participants' level of immunity against smallpox. Of the participants that have joined this ongoing study, six people were vaccinated within the last seven years while more than 100 were vaccinated between 15 and 67 years ago. His team is comparing the immunity of both groups to determine whether the vaccine truly loses potency over time.

This study looks at the effectiveness of both arms of the body's adaptive immune response: antibodies and T-cells. Blood samples from study participants are exposed to vaccina in petri dishes, the same virus used in the smallpox vaccine. If a person has strong immunity against vaccina, then his/her antibodies will neutralize the virus, thus saving healthy cells from becoming infected. If the virus is able to slip past this first line of defense and actually cause an infection, then a strong T-cell response is necessary to destroy virus-infected cells before they multiply and spread.

"In a petri dish, the vaccinia virus is typically very destructive and will eventually kill all of the cells that it encounters. However, if we mix blood serum of a vaccinated person with the virus before it can invade the first cell, then no damage occurs because the cells are protected against infection. Visually, weak immunity against smallpox looks in the petri dish like a lawn with a lot of dead patches of grass, while strong immunity results in a healthy "lawn" that has very few dead patches. With these and other techniques in hand, we can determine who has strong immunity and who has weak immunity following smallpox vaccination." said Slifka.

Scientists are studying the relationship between two levels of protection: protection against the disease and protection against death. The vaccine may prove to provide less protection against disease over time. In other words, a person might still get infected, but vaccination may still provide enough protection to lower the risk of death.

Another standard, but not proven, belief is that three or more vaccinations provide more immunity. Slifka's team also will look at the effectiveness of multiple vaccinations to determine if several vaccinations do build stronger immunity. Although most participants in this study have been vaccinated only once or twice, there are several volunteers that have been vaccinated between five and 11 times during their lifetimes.

Another research team at the VGTI and OHSU, led by Janko Nikolich-Zugich, M.D., Ph.D., and Mary Stenzel-Poore, Ph.D., is studying immunity to smallpox and vaccinia in people with weaker immune systems, such as the elderly, those on steroid therapy and those under significant stress. Using mice, they hope to discover specific defects in the immune system that prevent these immunocompromised individuals from receiving safe vaccinations against smallpox. Identifying these defects should help them develop re-engineered versions of the smallpox vaccine that can protect these vulnerable populations from this deadly disease. This group also will use Slifka's results to complement their research and help engineer new vaccines for the vulnerable populations.

Slifka also hopes to work with his co-investigator, Jon Hanifin, M.D., professor emeritus of dermatology in the OHSU School of Medicine, to develop a future study that will look at the weakened immune systems of people with eczema and other skin conditions who were vaccinated years ago, but by today's standards shouldn't have been vaccinated.

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SPECIFICS:
Mark Slifka, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine; assistant scientist at the OHSU Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center.

Janko Nikolich-Zugich, M.D., Ph.D., professor of molecular microbiology and immunology in the OHSU School of Medicine; senior scientist at the OHSU Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center.

Mary Stenzel-Poore, Ph.D., associate professor of molecular microbiology and immunology in the OHSU School of Medicine.

Jon Hanifin, M.D., professor emeritus of dermatology in the OHSU School of Medicine.

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