Targeting of different tissues via transcutaneous (TC), intradermal (ID) and
intramuscular (IM) injection has the potential to tailor the immune response
to DNA vaccination. In this Phase I randomised controlled clinical trial in
HIV-1 negative volunteers we investigate whether the site and mode of DNA
vaccination influences the quality of the cellular immune responses. We
adopted a strategy of concurrent immunization combining IM injection with
either ID or TC administration. As a third arm we assessed the response to IM
injection administered with electroporation (EP). The DNA plasmid encoded a
MultiHIV B clade fusion protein designed to induce cellular immunity. The
vaccine and regimens were well tolerated. We observed differential shaping of
vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses.
DNA given by IM + EP promoted strong IFN-γ responses and potent viral
inhibition. ID + IM without EP resulted in a similar pattern of response but
of lower magnitude. By contrast TC + IM (without EP) shifted responses towards
a more Th-17 dominated phenotype, associated with mucosal and epidermal
protection. Whilst preliminary, these results offer new perspectives for
differential shaping of desired cellular immunity required to fight the wide
range of complex and diverse infectious diseases and cancers