HE THREAT OF SMALLPOX BIOterrorism has prompted reconsideration of the need for smallpox vaccination. 1-3 Serious adverse events associated with firstgeneration vaccines such as the New York City Board of Health (Dryvax; Wyeth, Madison, New Jersey), Lister, and Ikeda strains 4-8 have raised obstacles to vaccination campaigns in the United States. 7-9 Second-generation vaccines such as ACAM2000 (Acambis, Cambridge, Massachusetts) that use a first-generation seed virus but are grown in tissue culture are also usually accompanied by a high frequency of adverse events. 10 Developing a vaccine that is safer than first-generation vaccines yet highly immunogenic is crucial to constructing a prevention plan in the event of bioterrorist attack. LC16m8 is a live, attenuated, tissuecultured third-generation vaccine comprising attenuated vaccinia virus strains as well as subunit vaccines made from viral proteins or DNA. 11 It is a desirable candidate for routine vaccination because of its low reactogenicity and reasonable safety profile. 12 Vaccination can be conveniently accomplished with a single intraepidermal scarification alone, which usually results in a visible major skin reaction ("take") similar to those resulting from first-and second-generation vaccines. 13 LC16m8 was derived from the Lister strain used for the Intensified Smallpox Eradication Programme of the World Health Organization 4 by temperature sensitivity and pock size See also Patient Page.

LC16m8 generates neutralizing antibody titers to multiple poxviruses, including vaccinia, monkeypox, and variola major, and broad T-cell responses, indicating that LC16m8 may have efficacy in protecting individuals from smallpox. Clinical Trials Registration. NCT00103584.

Posterior deep white matter in patients with PKU and a serum phenylalanine level of more than 8.5 mg/dL showed high signal intensity in white matter on T2-weighted and FLAIR MR images and revealed decreased ADC. We suggest that to avoid brain-restricted diffusion due to hyperphenylalanemia, patients with PKU should maintain serum phenylalanine levels of less than 8.5 mg/dL (514.2 micromol/L).

The licensed smallpox vaccine, ACAM2000, is a cell culture derivative of Dryvax. Both ACAM2000 and Dryvax are administered by skin scarification and can cause progressive vaccinia, with skin lesions that disseminate to distal sites. We have investigated the immunologic basis of the containment of vaccinia in the skin with the goal to identify safer vaccines for smallpox. Macaques were depleted systemically of T or B cells and vaccinated with either Dryvax or an attenuated vaccinia vaccine, LC16m8. B cell depletion did not affect the size of skin lesions induced by either vaccine. However, while depletion of both CD4(+) and CD8(+) T cells had no adverse effects on LC16m8-vaccinated animals, it caused progressive vaccinia in macaques immunized with Dryvax. As both Dryvax and LC16m8 vaccines protect healthy macaques from a lethal monkeypox intravenous challenge, our data identify LC16m8 as a safer and effective alternative to ACAM2000 and Dryvax vaccines for immunocompromised individuals.

The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the smallpox vaccine LC16-KAKETSUKEN in an adult population. LC16-KAKETSUKEN is the sole currently available licensed smallpox vaccine for both adult and pediatric populations.