Immunity from Smallpox Vaccine Persists for Decades: A Longitudinal Study

Abstract

PURPOSE-The threat of smallpox resulting from bioterrorist action has prompted a reassessment of the level of immunity in current populations. METHODS-We have examined the magnitude and duration of antiviral antibody immunity conferred by smallpox vaccination in 246 participants of the Baltimore Longitudinal Study of Aging.Of this population, 209 subjects were vaccinated one or more times 13 to 88 years before this evaluation, and stored serum samples were available at various intervals after vaccination. An additional 8 subjects who had documented childhood smallpox infection and 29 subjects with no history of infection or vaccination were included. We quantified the total vaccinia IgG and neutralizing antibody titers in each of these subgroups of participants over time.RESULTS-Vaccinated participants maintained antivaccinia IgG and neutralizing antibody titers above 3 natural logs essentially indefinitely. The absolute titer of antivaccinia antibody was only slightly higher after multiple vaccinations. In 97% of the participants, no decrease in vaccinia-specific antibody titers was noted with age over a follow-up period of up to 88 years. Moreover, Baltimore Longitudinal Study of Aging participants who survived active smallpox infections in their youth retained antivaccinia antibody titers that were similar to the levels detected in vaccinated subjects.CONCLUSION-These data suggest that multiple or recent vaccinations are not essential to maintain vaccinia-specific antibody responses in human subjects. Scarce vaccine supplies should be applied first to individuals who have not previously been vaccinated. KeywordsAging; BLSA; Biodefense; Smallpox; Vaccination; Vaccinia The vaccinia virus vaccine has been used to prevent smallpox disease and control its spread since the late 18 th century. Routine vaccination with vaccinia was discontinued over 30 years ago in many countries. [1][2][3][4][5][6][7][8] Despite the worldwide eradication of smallpox in 1977, the potential re-emergence of this disease from bioterrorist action has prompted international health care NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript authorities to reassess the level of immunity in current populations and to evaluate the risks and benefits of revaccination programs.Given that the majority of Americans under the age of 35 years have never been vaccinated against smallpox and the great majority of those over 35 have not received booster vaccinations since the early 1970s, immunity to smallpox is considered to be low to nonexistent in today's population. In the past, primary vaccination of individuals with vaccinia was believed to confer dependable protection for at least 5 years, with increasing protection achieved with subsequent revaccinations. 1,2 However, a major question posed today is whether those individuals vaccinated 40 or more years ago would be protected in the event of smallpox exposure. This may be a critical question because the availability of smallpox vaccines is limited and currently inade...

Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study

“…3). This is consistent with a previous study that found no differences in ELISA or neutralizing antibody titers between subjects who received smallpox vaccination and those who recovered from smallpox infection (35).…”

“…), we have an opportunity to measure the persistence of antiviral immunity to these two divergent orthopoxvirus infections in the relative absence of re-exposure/reinfection over a prolonged period of time. Although several studies have examined the duration of immunity following smallpox vaccination (2,4,9,17,31,35), little is known about the magnitude or duration of immunity following natural smallpox infection itself (32,35). This is an important question because smallpox infection is believed to confer lifelong protective immunity (5), whereas protective immunity following smallpox vaccination represents a topic of considerable debate; protective immunity is either long-lived (2,9,10,15,17,31,33,35) or may persist for only 3 to 5 years (19,21,26,28).…”

“…Prior studies have examined antibody levels (35) and/or T-cell responses (32) in a small number of smallpox-immune subjects with varying results. However, a formal case-control analysis of immunity following natural smallpox infection versus smallpox vaccination has not been previously performed, and this represents the objective of the present study.…”

Vaccine-Induced Protection against Orthopoxvirus Infection Is Mediated through the Combined Functions of CD4 T Cell-Dependent Antibody and CD8 T Cell Responses

“…The success of the smallpox vaccine is largely due to its being a live-virus vaccine that induces both cell-mediated and humoral immunity. Our understanding of immunity to smallpox in humans comes largely from prospective studies of the response to vaccinia virus (VACV) vaccination in humans (1)(2)(3)(4)(5)(6) and from animal studies using closely related orthopoxviruses (OPV), such as VACV (7,8), monkeypox virus (MPXV) (9)(10)(11), and ectromelia virus (ECTV) (12)(13)(14)(15). ECTV is a natural mouse pathogen that causes mousepox, a disease very similar to smallpox, and undoubtedly one of the best small-animal models available for investigating immunity to and pathogenesis of OPV infections (12-14, 16, 17).…”

Conventional Vaccine to Prevent AIDS A Paradigm or A Paradox? A SWOT Analysis

“…The cytolytic virus with its tropism and pathogenicity diminishes the memory by depleting the CD 4 [120]. Jenner's basis of immunization that imparts lifetime memory, conferred a hope to banish the small pox [121]. But in favor of the the virus, the viral quasispecies also has memory genomes to compete in their race with the host immune system [122,59].…”