Aug. 18, 2003 PORTLAND, Ore.– Final results of a smallpox vaccine study conducted by researchers at Oregon Health & Science University show America's preparedness for a smallpox outbreak may be greater than initially thought. The research shows 90 percent of those vaccinated 25 to 75 years ago maintain a substantial level of immunity. In addition, researchers concluded that in the long term, repeated vaccinations do not result in a higher level of disease protection. The research project is the largest of its kind ever conducted. The study is printed in the September edition of Nature Medicine.
"Previously, it had been widely accepted that smallpox virus effectiveness lasts only 3 to 5 years," said study principal investigator Mark Slifka, Ph.D., a scientist at the OHSU Vaccine and Gene Therapy Institute. "This research shows that significant immunity levels last for many decades, perhaps throughout a person's entire life. It also shows that repeated vaccinations provide a short-term boost in immunity but, over time, do not create a sustained higher level of protection compared to those persons vaccinated only once."
To conduct the research, OHSU enlisted the help of 332 study participants. Of this larger group, 306 participants had received at least one vaccination within their lifetime, some had undergone as many as 14 inoculations. The timing of vaccinations also varied among study volunteers. Some participants had been vaccinated as recently as one month prior to testing and as long ago as 75 years. The remaining 26 participants in the study had never received a smallpox vaccination in their lifetime and served as control subjects. The study group was very diverse; volunteers included those vaccinated in 43 states and 34 foreign countries.
"Some of our study participants had received repeated vaccinations. In one case, a person who at one time worked in a smallpox hospital had been vaccinated 14 times over their lifetime ," explained Slifka. "While many would assume this person would have a much higher level of immunity than a person only immunized once, we found this to be not necessarily the case."
Researchers also made key discoveries about long-term immune system responses following inoculation. They found that one component of the immune system retained memory of how to fight smallpox for a much longer period than another immune system component. One form of immunity is linked to levels of antibody produced in the body in response to the vaccine. In study participants, these antibody levels remained relatively stable up to 75 years post-vaccination. The second form of immunity is antiviral T-cells programmed by the vaccine to attack the smallpox virus. In study participants, antiviral T-cell levels declined slowly over time with a half-life of approximately 8 to 15 years.
"We found that while antibody immunity can last throughout a person's lifetime, T-cell immunity declines slowly over time," explained Slifka. "This may help explain curious findings in previously gathered data about vaccinated patients who became infected with smallpox at a later time."
Historical data suggests that immunity against lethal smallpox infection can be maintained for many years after vaccination. However, this same data also shows that the level of disease severity increases with the length of time between vaccination and infection – in other words more severe cases occur in infected patients vaccinated many years ago compared to infected patients vaccinated more recently. While Slifka says it's difficult at this point to state whether antibody or T-cell levels correspond to death and severity rates, the possibility of a connection exists.
The next step for Slifka and his colleagues is to track immune system responses for those recently vaccinated, the designated "first responders" in the case of a new outbreak. By studying these individuals, scientists will obtain a better understanding of how their immune systems respond over time and how varied the vaccine responses can be.
Slifka and his colleagues wish to thank those who assisted in gathering this research data, including the many local study volunteers, Washington County Public Health Officer Jay Kravitz, M.D., Clackamas County Health Officer Alan Melnick, M.D., and Multnomah County Health Officer Gary Oxman, M.D.
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