Smallpox Adjuvant Vaccine

Current approaches to vaccination for Smallpox have drawbacks due to the use of live vaccinia virus. While killed vaccinia virus-based smallpox vaccines have been proposed, none has proved entirely effective without the use of complex vaccination protocols or the addition of adjuvants that are unacceptable for humans.

We have determined the feasibility of a nanoemulsion-based killed vaccinia virus vaccine. This approach provides a rapid and effective means for a killed vaccinia virus vaccine.

We initially tested the ability of the nanoemulsion to inactivate vaccinia virus. We then evaluated the immunogenicity of vaccinia virus mixed with nanoemulsion placed into the nasal mucosa of mice. We characterized the immune responses and determined that mice immunized with vaccinia/nanoemulsion developed protective immunity. Our data suggests that the mucosal route of immunization with nanoemulsion-killed virus is particularly suitable for the effective generation of antibodies for the critical viral epitopes (similar to those in live virus), but without infection, and it may lead to protective immunity from infection with live vaccinia virus. This was confirmed by a challenge test in mice immunized with the nanoemulsion-vaccinia mixture as well as non-immunized mice which were exposed to infection with live vaccinia virus

graph of vaccination with mucosal nanoemulsion-based killed VAC vaccine in mice — Balb/c mice were immunized with three intranasal administrations of 105 pfu of the nanoemulsion-killed Vaccinia virus WR serotype (VAC). After the course of vaccination, both treated and control mice were intranasally infected with a 10-fold multiplication of the lethal dose (LD = 2 x 105 pfu) of live VAC virus. All non-vaccinated animals died in 4 to 7 days after the challenge, while none of the vaccinated mice died during the three weeks of the experiment or beyond.

This work has been supported by the National Institutes of Health via the Region V Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research.