AMPLIFICATION OF T-CELL AND ANTIBODY-RESPONSES IN DNA-BASED IMMUNIZATION WITH HIV-1 NEF BY COINJECTION WITH A GM-CSF EXPRESSION VECTOR

Intradermal inoculation of mice with naked plasmid DNA encoding the re gulatory HIV-1 Nef protein was shown to induce Nef-specific T and B ce ll responses. Co-inoculation with an expression vector encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine known to facilitate the induction of primary immune responses, result ed in a markedly enhanced response to Nef. This was manifested both as an increase in Nef-specific T cell responses and antibody levels. DNA immunization with the Nef and GM-CSF vectors induced primarily a Th1 response as judged by the raised levels of both IFN-gamma and IL-2, fr om re-stimulated T cells. The immunostimulatory activity of GM-CSF DNA was locally restricted and was observed only if both plasmid vectors were injected at the same site.