Writing in the Aug. 29 issue of The New England Journal of Medicine, Dr. Jeffrey A. Frelinger, Kenan professor and chairman of microbiology and immunology in the School of Medicine, and postdoctoral researcher Dr. Lawal Garba said despite substantial interest today "in the durability of immune responses following smallpox vaccination," little direct or quantifiable evidence of such durability exists.
"It's a question that's been largely unexamined," said Frelinger, who mentioned reports suggesting that the standard vaccine, which contains live vaccinia virus but not smallpox, or variola, virus, could protect against lethal infection in people vaccinated 50 years previously.
Vaccinia vaccine triggers an immune response to orthopoxviruses that can infect humans, such as monkeypox, cowpox, vaccinia and variola. During the course of another investigation, Frelinger and Garba tested blood samples from 13 laboratory workers who had been vaccinated according to federal guidelines because they work with vaccinia virus. Four had been vaccinated less than five years ago. Another nine individuals had been vaccinated either between five and 35 years previously or more than 35 years ago.
The researchers tested the strength of each individual's CD8 T cell response to vaccinia exposure by counting the number of cells that respond to vaccinia by production of interferon-gamma.
In the body's cellular immune response, CD8 T cells are a type of cytotoxic T lymphocyte, or CTL, white cells that kill other body cells that have been infected by a foreign organism. CTLs recognize surface markers on other cells in the body that label those cells for destruction. In this way, CTLs help keep virus-infected cells in check. CD8 T cells produce interferon-gamma and other molecules that are protective in viral infections.
"Given the general belief that the vaccinations lasted only seven to 10 years, we were surprised how durable the CTL responses were," Frelinger said.
In their letter to the journal, Frelinger and Garba said "two observations are obvious, vaccinia induces a robust CD8 T lymphocyte response in healthy individuals and, second, the response is of long duration."
Testing showed that the cells of individuals who were vaccinated decades ago still reacted to vaccinia by making interferon-gamma, but at a slightly lower level.
"It is striking that the loss of reactivity over more than 35 years is very low … in individuals with a remote history of vaccination compared to recently vaccinated individuals," the authors wrote. Quantitatively, 4.8 percent of CD8 cells in individuals vaccinated more than 35 years ago reacted to vaccinia by producing interferon-gamma, compared to 6.5 percent of CD8 cells in recently vaccinated individuals.
"Resistance to vaccinia is waning but not rapidly. It is still substantial," Frelinger said. "We would think that people even 35 years later would still have substantial resistance to smallpox infection."
Frelinger said such long-lasting protection would have implications for devising a smallpox vaccination strategy. "If you had a limited supply of vaccine, I think you'd want to target predominantly previously unvaccinated individuals."
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