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September 2003 • Volume 37 • Number 9

Infectious Diseases

Degrades only slightly over time
Smallpox Vaccine May Provide Lifelong Immunity

Joyce Frieden
Associate Editor, Practice Trends

Contrary to popular belief, the smallpox vaccine appears to provide lifelong immunity, according to Erika Hammarlund of the Oregon Health & Science University Vaccine and Gene Therapy Institute in Beaverton, and her associates.

The researchers studied 306 vaccinees at 1-75 years after their first vaccination and 26 unvaccinated controls. Vaccinees had been immunized anywhere from 1 to 14 times (Nat. Med. Advance Online Publication, Aug. 17, 2003).

To determine the vaccinees' response to the vaccine, the researchers looked at the patients' CD4 T-cell responses using a staining protocol that detects vaccinia-specific T cells by virtue of their ability to produce potent antiviral factors such as interferon and tumor necrosis factor. They also looked at CD8 T-cell responses using ex vivo stimulation with vaccinia-infected cells.

“Direct comparisons between virus-specific CD4 and CD8 T-cell numbers within individual vaccinees revealed dynamic and independently regulated changes in T-cell memory over time,” they said. “At early time points ranging from 27 days to 7 years after vaccination, nearly all volunteers possessed strong CD4 and CD8 T-cell responses.”

Later on—anywhere from 14 to 75 years after vaccination—many individuals still maintained both CD4 and CD8 T-cell memory, although at lower levels than before.

However, other patients “preferentially lost” CD8 T-cell memory “while leaving the antiviral CD4 T-cell compartment intact,” they noted.

The researchers also used a vaccinia-specific ELISA test to look at serum antibody levels over time.

“In contrast to vaccinia-specific T-cell memory, which declined steadily over time, vaccinia-specific serum antibody levels were remarkably stable between 1 and 75 years after vaccination,” the researchers said.

Looking at the effect of multiple vaccinations, they found although vaccinees generally showed a slight increase in antibody titer after a second vaccination, additional vaccinations—anywhere from 1 to 12 more—did not result in any further increase in long-term antibody production.

“This indicates that booster vaccination may increase a previously suboptimal antibody response but is unlikely to induce prolonged synthesis of higher antibody numbers above a certain threshold,” the investigators noted.

They also did not find any correlation between virus-specific T-cell numbers and antibody titers, indicating that humoral and cellular immunity were regulated independently.

“Immunity against smallpox has been believed to persist for only 3-5 years after vaccination,” according to Ms. Hammarlund and her associates. “But contrary to this perspective, several large epidemiological studies have shown that smallpox vaccination provided 90%-95% of vaccinees with protection against lethal smallpox infection for many years and possibly for life. … Our study demonstrates that more than 90% of volunteers maintain measurable humoral or T-cell-mediated immunity for up to 75 years after smallpox vaccination—a result that will affect future models of potential smallpox outbreaks in contemporary populations.”