Risk of Vaccinia Transfer to the Hands of Vaccinated Persons after Smallpox Immunization

Talbot, Thomas R.; Ziel, E.; Doersam, Jennifer K.; LaFleur, Bonnie; Edwards, Kathryn M.

doi:10.1086/381205

Cited by 28 publications

(19 citation statements)

References 8 publications

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“…Due to the concern of inadvertent VV autoinoculation and transmission to contacts of smallpox vaccine recipients, covering the site of inoculation with semipermeable dressings and paying careful attention to dressing care and hand hygiene is recommended until scabs separate (24). The significant impact of ST-246 treatment on virus shedding in the respiratory tract (Fig.…”

Section: Vv-infected Mice Are Protected From Virus-induced Systemic Dmentioning

confidence: 99%

ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation

Berhanu

King

Mosier

et al. 2009

Antimicrob Agents Chemother

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Orthopoxvirus infections, such as smallpox, can lead to severe systemic disease and result in considerable morbidity and mortality in immunologically naïve individuals. Treatment with ST-246, a small-molecule inhibitor of virus egress, has been shown to provide protection against severe disease and death induced by several members of the poxvirus family, including vaccinia, variola, and monkeypox viruses. Here, we show that ST-246 treatment not only results in the significant inhibition of vaccinia virus dissemination from the site of inoculation to distal organs, such as the spleen and liver, but also reduces the viral load in organs targeted by the dissemination. In mice intranasally infected with vaccinia virus, virus shedding from the nasal and lung mucosa was significantly lower (ϳ22-and 528-fold, respectively) upon ST-246 treatment. Consequently, virus dissemination from the nasal site of replication to the lung also was dramatically reduced, as evidenced by a 179-fold difference in virus levels in nasal versus bronchoalveolar lavage. Furthermore, in ACAM2000-immunized mice, vaccination site swabs showed that ST-246 treatment results in a major (ϳ3,900-fold by day 21) reduction in virus detected at the outside surfaces of lesions. Taken together, these data suggest that ST-246 would play a dual protective role if used during a smallpox bioterrorist attack. First, ST-246 would provide therapeutic benefit by reducing the disease burden and lethality in infected individuals. Second, by reducing virus shedding from those prophylactically immunized with a smallpox vaccine or harboring variola virus infection, ST-246 could reduce the risk of virus transmission to susceptible contacts.Smallpox disease is marked by the dissemination of variola virus within the infected host and the appearance of skin lesions or pocks (reviewed in reference 3 and at http://whqlibdoc .who.int/smallpox/9241561106.pdf). The virus is transmitted between humans mainly by aerosol droplets; however, contact with variola virus-contaminated clothing or bedding may contribute to transmission. Once inhaled, variola virus appears to first infect the upper-or lower-respiratory-tract mucosa and spread to and replicate within the local lymph nodes. The virus then disseminates to the spleen and liver via a transient viremia and replicates in reticuloendothelial cells through an average incubation period of 10 to 12 days. During the high-fever prodrome period that follows, a second wave of viremia occurs and results in the dissemination of the virus to mucous membranes of the mouth and pharynx and to the dermal epithelium of the skin. This dissemination leads to the eruption of lesions over the tongue, mouth, and oropharynx and of rashes that start at the face and extremities and may eventually envelope the whole body. Studies performed for 2 to 3 weeks after the onset of fever indicated that infectious virus is excreted in the throat, urine, and conjunctiva of smallpox patients (20). Additionally, the level and duration of secretion was higher in ...

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Section: Vv-infected Mice Are Protected From Virus-induced Systemic Dmentioning

confidence: 99%

ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation

Berhanu

King

Mosier

et al. 2009

Antimicrob Agents Chemother

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“…Virus titers from the site of vaccinia inoculation were determined, as described (22). Briefly, samples for viral culture were obtained from each subject at each of the scheduled follow-up visits after immunization.…”

Section: Viral Culturementioning

confidence: 99%

Differential Regulation of Granzyme and Perforin in Effector and Memory T Cells following Smallpox Immunization

Rock

Yoder²,

Wright

et al. 2005

The Journal of Immunology

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Primary immunization of healthy adults with vaccinia virus induces a local vesicle or “take” in the majority of vaccinees that previously has been shown to correlate with protection against smallpox. However, the immunologic mechanisms underlying this protective response in humans are not well characterized. We have studied human CD8+ T cells for the expression patterns of phenotypic markers and cytolytic effector molecules before and after primary smallpox immunization using nine-color polychromatic flow cytometry. One month after immunization, vaccinees developed vaccinia virus-specific CD8+ T cells with an effector cell phenotype containing both granzyme A and granzyme B. One year after immunization, we found a significant decrease in granzyme B containing cells and an increased memory cell phenotype in virus-specific CD8+ T cells. Perforin was rarely expressed directly ex vivo, but was highly expressed after Ag-specific activation in vitro. Together, these data suggest an important role for effector CD8+ T cells in controlling poxvirus infection, and have implications for our understanding of human CD8+ T cell differentiation.

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“…Even touching the skin rash or vaccination site can result in the spread of the vaccinia virus to persons in contact with it (contact transmission). Some Dryvaxvaccinated persons can even develop serious side effects, such as lymphadenopathy, vaccinia dissemination, eye infection, postvaccinial encephalitis, permanent disability, life-threatening illness, or death (19,20,34,35). Furthermore, recent data from clinical monitoring suggest that vaccination with replicating vaccinia virus can induce adverse cardiovascular events (30,33).…”

mentioning

confidence: 99%

Coadministration of Cidofovir and Smallpox Vaccine Reduced Vaccination Side Effects but Interfered with Vaccine-Elicited Immune Responses and Immunity to Monkeypox

Wei

Huang

Fortman

et al. 2009

J Virol

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While the smallpox vaccine, Dryvax or Dryvax-derived ACAM2000, holds potential for public immunization against the spread of smallpox by bioterror, there is serious concern about Dryvax-mediated side effects. Here, we report that a single-dose vaccination regimen comprised of Dryvax and an antiviral agent, cidofovir, could reduce vaccinia viral loads after vaccination and significantly control Dryvax vaccination side effects. However, coadministration of cidofovir and Dryvax also reduced vaccine-elicited immune responses of antibody and T effector cells despite the fact that the reduced priming could be boosted as a recall response after monkeypox virus challenge. Evaluations of four different aspects of vaccine efficacy showed that coadministration of cidofovir and Dryvax compromised the Dryvax-induced immunity against monkeypox, although the covaccinated monkeys exhibited measurable protection against monkeypox compared to that of naïve controls. Thus, the single-dose coadministration of cidofovir and Dryvax effectively controlled vaccination side effects but significantly compromised vaccine-elicited immune responses and vaccine-induced immunity to monkeypox.

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Risk of Vaccinia Transfer to the Hands of Vaccinated Persons after Smallpox Immunization

Cited by 28 publications

References 8 publications

ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation

ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation

Differential Regulation of Granzyme and Perforin in Effector and Memory T Cells following Smallpox Immunization

Coadministration of Cidofovir and Smallpox Vaccine Reduced Vaccination Side Effects but Interfered with Vaccine-Elicited Immune Responses and Immunity to Monkeypox

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