Deletion of immunomodulator C6 from vaccinia virus strain Western Reserve enhances virus immunogenicity and vaccine efficacy

Vectors based on vaccinia virus (VACV), the vaccine used to eradicate smallpox, are currently popular candidates for the vaccination against numerous infectious diseases including malaria and AIDS. Although VACV induces robust cellular and humoral responses, enhancing the safety and efficacy of these vectors remains an important area of research. Here, we describe the enhanced immunogenicity of a recombinant VACV Western Reserve (WR) strain lacking the immunomodulatory protein C6 (v Delta C6). Intradermal infection of mice with v Delta C6 was shown previously to induce smaller lesions, indicating viral attenuation, and this was confirmed here using a different inoculation dose. In addition, data presented show that vaccination with v Delta C6 provided better protection against challenge with a lethal dose of VACV WR, indicating this virus is a better vaccine. Increased protection was not due to improved humoral responses, but instead enhanced cytotoxic activity of 1-cells 1 month post-inoculation in the spleens of v Delta C6-vaccinated mice.