Duration of Antiviral Immunity After Smallpox Vaccination

Abstract & Commentary

Synopsis: More than 90% of individuals studied maintain measurable humoral or T-cell-mediated immunity against vaccinia virus for as long as 75 years after smallpox vaccination.

Source: Hammarlund E, et al. Nature Med. 2003;9: 1131-1137.

Hammarlund and colleagues at the University of Oregon examined a group of individuals who had received smallpox vaccination 1-75 years previously in order to determine the duration and magnitude of immunity against vaccinia virus. The in vitro studies performed included the quantification of virus-specific CD4+ and CD8+ lymphocyte responses as well as of neutralizing antibody.

More than 90% of volunteers who had been vaccinated 1-75 years previously had evidence of substantial humoral and/or cellular immunity against vaccinia. While antiviral T-cell responses declined slowly over time with a half-life of 8-15 years, antibody responses remained stable for 1-75 years after vaccination.

Comment by Stan Deresinski, MD, FACP

The duration of immunity after receipt of vaccinia has been a matter of some discussion. Often accepted is a duration of only 3-5 years, and this was the figure that was used in the structuring of the vaccination program recently held in abeyance by the United States. Mack, however, cites a number of epidemiological studies that suggest the period of protection is many years longer, with at least 90-95% protection against lethal infection for more than 20 years after vaccination.1 This is consistent with the long-term immunity induced by other live attenuated virus vaccines.

The nationwide smallpox vaccination program was recently halted. The vaccine had been offered to the approximately 2.5 million health care professionals and technicians working in US hospitals. Based on previous estimates of risk, at least 7-8 vaccine-related deaths were expected.2,3 The vaccine was offered regardless of prior vaccination—more than 90% of Americans older than 35 have been vaccinated against smallpox, mostly as infants. However, by the end of March 2003, only 25,645 public health and health care workers in the United States had been vaccinated. Many health care workers opted out of the program for a number of reasons, including the reports of the occurrence of myocarditis and cardiac deaths in a small number of vaccine recipients. For many health care workers who chose to not be vaccinated, it is likely that their calculus was something like the following: While the risk of an attack is unknowable, there have been no cases. There is some risk from vaccination. Postexposure vaccination, especially combined with vaccinia immune globulin, is quite effective in prevention of severe disease.

The program also proved costly in terms of dollars. In April, the Association of State and Territorial Health Officials estimated the average cost of a single vaccination to be $249, with the cost ranging from $79 in Tennessee to more than $1000 in Hawaii and Alaska. Randy Cohen in his column on ethics in the New York Times Sunday Magazine (Jan 19, 2003, page 18) pointed out another aspect of this issue. "Financing an expensive smallpox vaccination program necessarily means neglecting many pressing medical problems, both here and abroad. In our era of tight budgets, deciding how to allocate health care resources is a question with both moral and political implications." In other words, is it moral to spend large amounts of money on a problem, which we may never confront, or on ones, such as malaria and diarrheal illness that kill children every day?

Dr. Deresinski is Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, Santa Clara, Calif.


1. Mack TM. Smallpox in Europe, 1950-1971. J Infect Dis. 1975;125:161-169.

2. Bozzette SA. N Engl J Med. 2003;348:416-425.

3. Mack T. N Engl J Med. 2003;348:460-463.