Recombinant vaccinia virus expressing the PR/8 influenza hemagglutinin gene overcomes the impaired immune response and increased susceptibility of old mice to influenza infection.

Elderly humans have increased morbidity and mortality after viral influenza despite immunization. A mouse model of influenza infection was used to search for a more effective way to induce immunity to influenza. Old (18 months) BALB/c mice were more susceptible to influenza pneumonia than young (2 months) BALB/c mice after intranasal challenge with PR/8 influenza virus despite prior immunization with influenza virus. The decreased resistance to live influenza virus challenge was associated with an impaired generation of anti-hemagglutinin antibody and cytotoxic T lymphocytes in old mice. In contrast, immunization of old mice with a recombinant vaccinia virus expressing the PR/8 influenza hemagglutinin gene protected them from intranasal challenge with live influenza virus and generated high levels of anti-PR/8 influenza virus hemagglutinin antibody and PR/8-specific cytotoxic T cells. Recombinant vaccine overcame the age-associated immune defect that follows the administration of conventional viral vaccine.