Plasmid DNA encoding the respiratory syncytial virus G protein is a promising vaccine candidate

Respiratory syncytial virus (RSV) remains a major cause of severe respirato ry diseases in infants, young children, and the elderly. However, developme nt of a RSV vaccine has been hampered by the outcome of the infant trials i n the 1960s with a formalin-inactivated RSV preparation. Enhanced lung dise ase was induced by the Vaccination post-RSV exposure. Previous studies in m ice primed with RSV G protein either formulated in adjuvants or delivered b y recombinant vaccinia viruses have indicated that enhanced lung pathology resulted from a Th2-type host immune response against the viral G protein. However, in the present report, we have demonstrated that vaccination with plasmid vectors encoding either a full-length or a secreted G protein (DNA- G) clearly elicited balanced systemic and pulmonary Th1/TH2 cytokine respon ses in mice and did not induce an atypical pulmonary inflammatory reaction post-RSV challenge in cotton rats. DNA-G immunization also induced marked v irus neutralizing antibody responses and protection against RSV infection o f the lower respiratory tract of both mice and cotton rats. So far, only ge netic immunization has been able to induce a balanced Th1/Th2 response with the RSV G protein, reminiscent of that induced by live RSV. Therefore, DNA -G is a promising immunogen for inclusion in a nucleic acid RSV vaccine. (C ) 2000 Academic Press.