Enhancement of antibody responses by DNA immunization using expression vectors mediating efficient antigen secretion

The immune responses elicited in mice, after intradermal (i.d.) immunizatio n with plasmids encoding secreted or intracellular forms of HIV-1 nef, HIV- 1 rat or C. pneumoniae omp2 proteins, respectively, were compared. To media te secretion of these proteins the genes were fused to a heterologous signa l sequence from murine heavy chain IgG. The nef- and omp2-specific antibody responses were dramatically increased when mice were inoculated with the p lasmid encoding the secreted form of these proteins. In contrast, HIV-1 tar comprising an internal strong nuclear targeting sequence could not be indu ced to secretion and subsequently no enhanced antibody response was observe d. Slight improvement of the HIV-1 nef antibody response was achieved after co-inoculation with a granulocyte-macrophage colony stimulating factor (GM -CSF) expression vector. Further, nef-specific T-cell responses were induce d after nef DNA injections, and were of Th1-like phenotype regardless of wh ether the nef protein was secreted or not. The system described in this stu dy, using a plasmid vector with a strong heterologous signal sequence that mediate efficient antigen secretion in vivo, may have wide applicability fo r the induction of high antibody levels to normally non-secreted antigens. (C) 1999 Elsevier Science B.V. All rights reserved.