An Old Weapon May Still Be Effective in the War Against Bioterrorism – Smallpox Vaccination

In recent years, there has been renewed interest in creating new smallpox vaccines due to the threat of the smallpox pathogen being used as a bioterrorism tool. The vaccinia virus vaccine has been used to prevent smallpox disease since the late 18th century and, until 30 years ago, most countries conducted routine smallpox vaccination programs. Thanks to these efforts, smallpox was virtually eradicated from the world by 1977, and many countries discontinued the vaccination programs. For this reason, most Americans under 35 years of age have never had smallpox disease, nor been vaccinated against the disease, making immunity effectively nonexistent in today’s population.

Smallpox has been a bioterrorism threat for many years, but has garnered more attention since 2001. The potential comeback of smallpox, coupled with a lack of immunity and a limited supply of existing vaccine, makes this threat all the more frightening. Advances are underway to create a new, improved smallpox vaccine to prepare for a biological terror attack or disease outbreak. The long-held belief and recommendation is that people with repeated risk of exposure to smallpox should be revaccinated every 5 years. As with most vaccines, it was believed that immunity to smallpox decreased over time after inoculation with the vaccine. People who survived a natural course of the disease carry lifelong immunity to smallpox.

However, a new study published in the American Journal of Medicine suggests otherwise. In order to evaluate the long-term immunity conferred by the smallpox vaccine, researchers examined 246 subjects enrolled in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA was established in 1958 to study normal aging processes and gather information on health and psychological function. Individuals vary in age, and are re-evaluated every 1 to 5 years. Of the 246 subjects examined, 209 had been vaccinated with smallpox vaccine at least once in the past. Time since vaccination ranged from 13 to 88 years. Eight of the subjects had documented smallpox infections as children, and 29 subjects had no history of infection or vaccination.

Surprisingly, the vaccinated participants maintained effective immunity against smallpox indefinitely, measured by levels of antibody titers. The vaccine titers were only slightly higher in people who received multiple vaccinations, though this finding does not appear to be clinically significant. Also unexpectedly, the levels of antibody titers were similar in people who had received vaccines and those who had experienced a childhood infection of smallpox. The researchers suggest that not only are multiple vaccinations not necessary, but also that recent vaccinations are not necessary to maintain smallpox immunity. One vaccination may last a lifetime. They suggest that the small supply of vaccine available should be given to individuals who have not been previously vaccinated or experienced a smallpox infection, rather than re-vaccinating at-risk individuals.

There is still a need for enhanced smallpox vaccines, since the safe vaccination of special populations needs to be addressed, as well as the risk of morbidity and mortality associated with the disease and the current vaccine. The limited supply of available vaccine makes complete protection of the at-risk population impossible. However, while we wait for newer generation vaccines to become available, the current supply may be more effective than we first thought in protecting at least some individuals.


Andrew W. Artenstein (2008). New generation smallpox vaccines: a review of preclinical and clinical data Reviews in Medical Virology, 18 (4), 217-231 DOI: 10.1002/rmv.571

A GARCEL, J PERINO, J CRANCE, R DRILLIEN, D GARIN, A FAVIER (2008). Phenotypic and genetic diversity of the traditional Lister smallpox vaccine Vaccine DOI: 10.1016/j.vaccine.2008.11.063

D TAUB, W ERSHLER, M JANOWSKI, A ARTZ, M KEY, J MCKELVEY, D MULLER, B MOSS, L FERRUCCI, P DUFFEY (2008). Immunity from Smallpox Vaccine Persists for Decades: A Longitudinal Study The American Journal of Medicine, 121 (12), 1058-1064 DOI: 10.1016/j.amjmed.2008.08.019

Wharton M, Strikas RA, Harpaz R, et al. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. Apr 4 2003;52(RR-7):1-16.

Jennifer Gibson, PharmD

Jennifer Gibson, PharmD, is a practicing clinical pharmacist and medical writer/editor with experience in researching and preparing scientific publications, developing public relations materials, creating educational resources and presentations, and editing technical manuscripts. She is the owner of Excalibur Scientific, LLC.
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