HIV-1 remains a major public health problem all over the world despite efficacious antiviral therapies, but in absence of a vaccine. We developed an innovative lentiDNA vaccine based on the backbone of SHIV-KU2, lacking the integrase gene. In our earlier studies we demonstrated persistent Gag- and Nef-specific CD4+ and CD8+ T precursors (PHPC), central memory (Tcm) and effector memory (Tem) cells up to 80 weeks post-immunization in Cynomolgus macaques. To evaluate whether these memory pools of cells can be amplified, a cassette containing IL-7 or IL-15 gene was inserted into the lentiDNA. Humoral and cellular responses elicited by the two co-injected lentiDNA-IL-7 and lentiDNA-IL15 were compared with those elicited by the parental lentiDNA.
BALB/c mice and Rhesus macaques were immunized by intradermal route with electroporation and intramuscularly with 100 µg (mice) and 5 mg (macaques) plasmid DNA respectively. Mice and macaques received homologous boosts at 6 and 16 weeks post-immunization, respectively. IFN-? ELISPOT was evaluated on mouse splenocytes and macaques PBMCs and cells of draining lymph nodes respectively. Vaccine specific antibody responses and their functions were examined in serum and rectal secretions. Median values were used for each group, and statistical analyses were done by using unpaired T-test.
We found that co-administered lentiDNA-IL-7 and lentiDNA-IL-15 elicited potent Gag- and Nef-specific CD4+ and CD8+ T cells in mice and macaques. The follow-up up to 40 weeks in macaques highlighted the long-term response capacity. Also, Gag-specific Tcm and Tem secreting Granzyme B and MIP-1? were enhanced. Furthermore, non-neutralizing plasma IgG antibodies with ADCC function as well as strong mucosal IgA responses were detected up to 40 weeks post-immunization and enhanced by the adjuvant cytokines in macaques.
In summary, co-expression of IL-7 and IL-15 with antigens of our lentiDNA vaccine resulted in augmented proportion and longevity of vaccine-specific CD4+ and CD8+ memory T cells in mouse spleen cells and macaque PBMCs. Concomitantly it also elicited long-lasting responses of plasma IgG together with mucosal IgA and IgG in rectal secretions.