Immune memory after smallpox vaccination persists for at least 50 years in immunized individuals, according to research conducted by scientists at the Emory Vaccine Center (EVC) and the School of Medicine. This is good news, since the findings, published in the Nov. 15 issue of the Journal of Immunology, suggest that individuals vaccinated against smallpox prior to the end of the smallpox vaccination program in 1972 may still retain at least some protection.

Rafi Ahmed, Georgia Research Alliance Eminent Scholar and EVC director, was principal investigator of the study, and Shane Crotty, formerly in the School of Medicine and currently a faculty member at The La Jolla Institute for Allergy and Immunology, was first author. Emory microbiologist John Glidewell also was a member of the research team.

Although scientists have known that acute viral infections and vaccines produce two types of long-term immune memory that provide protection against disease, they still are learning the details of these immune mechanisms.

Using a new blood test they developed to assess human antigen-specific immunity, the scientists measured memory B cell responses in individuals recently vaccinated with smallpox vaccine (DryVax), in unvaccinated individuals and in individuals vaccinated between three months and 60 years earlier.

The recently vaccinated group showed a significant virus-specific memory B cell response to vaccinia, while the unvaccinated individuals were negative for vaccinia virus-specific memory B cells. Vaccinia virus-specific B cells were detected in most of the previously vaccinated individuals in the study, including those vaccinated up to 60 years earlier.

The scientists found that virus-specific memory B cells initially declined after smallpox immunization but reached a plateau approximately 10 times lower than their peak, where they remained stable for more than 50 years. Although there were significantly fewer memory B cells in the most recently vaccinated group compared to those vaccinated decades earlier, there was no significant change in B cell memory between 20 and 60 years after vaccination. In addition, individuals vaccinated against smallpox maintained antismallpox antibodies in their blood for at least 60 years after vaccination, with no indication of decline between one and 60 years.

In humoral immunity, the body’s first line of defense against infection is antibodies produced by B cells, which are the primary measure of immunity for most vaccines. Memory B cells are responsible for stimulating a rapid antibody response after re-exposure to infection. In cellular immunity, activated T cells kill specific virus-infected cells and also produce cytokines (proteins that prevent the growth of viruses and make cells resistant to viral infection). Ahmed’s previous studies in mice showed that B cell memory can persist even without re-exposure to viral antigens, but this had not yet been demonstrated in humans.

In order to test the functionality of the memory B cells, the scientists revaccinated a group of test subjects who had been vaccinated between 22 and 48 years earlier, and detected twentyfold increases in vaccinia-virus antibodies after the second vaccination. They also tested antibody response to a specific viral protein. In previously immunized individuals they detected an antibody response prior to booster immunization as well as a strong response four weeks after booster immunization. In newly vaccinated individuals, however, the antibody response to the specific viral protein was virtually undetectable.

"Immune memory to smallpox vaccination is an excellent benchmark to help us understand the mechanisms of good vaccines and also to understand the longevity and stability of immune memory in the absence of revaccination or disease," Ahmed said. "Our findings may be useful as decisions are made about reinstituting a smallpox vaccination program. And because smallpox has an incubation period of from 12–14 days, this provides a window of opportunity for memory B and T cells to expand and attack the infection before the onset of clinical disease."