Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.
These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.
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...
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