DIFFERING T-CELL REQUIREMENTS FOR RECOMBINANT RETROVIRUS VACCINES

Friend murine leukemia virus is a retrovirus complex that induces rapi d erythroleukemia and immunosuppression in susceptible strains of adul t mice. Using this model, we directly examined the T-cell subsets requ ired for a protective retrovirus vaccine. Paradoxically, recovery in m ice immunized with a chimeric envelope containing only T-helper (T-H) and B-cell epitopes was dependent on CD8(+) T cells as well as CD4(+) T cells despite the fact that the vaccine contained no CD8(+) cytolyti c T-Lymphocyte (CTL) epitopes, However, the requirement for CD8(+) T c ells was overcome by inclusion of additional T-H and B-cell epitopes i n the immunizing protein. These additional epitopes primed for more ra pid production of virus-neutralizing antibody which appeared to limit virus spread sufficiently to protect even in the absence of CD8(+) T c ells. Inclusion of an immunodominant CTL epitope in the vaccine was no t sufficient to overcome dependence on CD4(+) T cells, These data sugg est that T-H priming is more critical for retrovirus immunity than CTL priming.