Alternative immunological markers to document successful multiple smallpox revaccinations.

BACKGROUND: Successful smallpox vaccination is traditionally defined by clinical response ("take"). Nevertheless, only 60% of subjects in the 2002 Israeli smallpox revaccination campaign developed clinical take. More sensitive immunological markers are needed to document successful revaccination. We compared the level of vaccinia-specific immune markers among subjects who did or did not develop clinical take following revaccination. METHODS: Forty subjects who participated in 2002 smallpox revaccination campaign and developed clinical take were individually matched for age, sex, and smallpox vaccinations with subjects who did not develop clinical take ("no-take"). Vaccinia immunity markers were examined prior to and 14 days and 2 years after revaccination. RESULTS: Higher levels of total immunoglobulin (Ig) G, IgG1, and neutralizing antibodies (highest dilution of serum that inhibited the cytopathic effect by at least 50% [PRNT50]) were observed in the no-take group before vaccination (166 vs 94.3 ELISAU/mL [P<.05], 53.2 vs 34.5 ELISAU/mL [ P<.05], and 30% vs 19.7% [P<.05], respectively). The mean time since last smallpox vaccination was longer in the take group than in the no-take group. Total IgG, IgG subclasses, avidity index, and PRNT50 levels were higher among "take" than "no-take" volunteers 14 days after revaccination. The no-take group was not inferior to the take group in all vaccinia immune marker levels measured 24 months after vaccination. Moreover, mean interferon-γ secretion and the percentage of serum samples with PRNT50 levels ≥1:32 were significantly higher in the No-take group than in the take group (677.5 vs 282.7 pg/mL [P < .05] and 95% vs 80% [P<.05], respectively). CONCLUSIONS: The overwhelming majority of subjects in the no-take group were successfully revaccinated against smallpox. Under circumstances of emergent smallpox mass immunization, there is no need for revaccination success assessment among individuals who have received multiple previous smallpox vaccinations.

Immunosuppressive treatments reduce long-term immunity to smallpox among patients with breast cancer.

BACKGROUND: Mass vaccination is the principal preventive measure against a smallpox outbreak after an act of bioterrorism. Vaccination of subjects who received immunosuppressive therapies is problematic because of smallpox vaccine reactogenicity. Moreover, long-term immunity to vaccinia might be affected. OBJECTIVE: The objective of the study was to examine the effect of cytotoxic chemotherapy on long-term immunity to vaccinia. METHODS: In a case-control study, 67 patients with breast cancer who received cytotoxic chemotherapy and who were disease free for at least 1 year were matched with healthy controls according to age, sex, and the number of smallpox vaccinations received. Markers of immunity to smallpox were examined. Forty-one patients with breast cancer who did not receive chemotherapy were used to assess the affect of cancer and radiotherapy on immunity to smallpox. RESULTS: Patients with breast cancer who received chemotherapy had lower levels of vaccinia total immunoglobulin G and immunoglobulin G1 (expressed as enzyme-linked immunosorbent assay units per milliliter), neutralizing antibodies, vaccinia:memory B cell ratio (expressed as a percentage), and interferon-gamma level (expressed as picograms per milliliter), compared with healthy control individuals. CONCLUSIONS: Immunity to smallpox is reduced after receipt of chemotherapy for breast cancer. This finding should be considered when planning smallpox vaccination campaigns. The effect of immunosuppressive treatments on persistence of immunity should be tested with respect to additional vaccines or natural infections.