P41.15
Background: We have developed αCD40.HIV5pep and αDCIR.HIV5pep, two dendritic cell (DC)-targeting vaccines, containing 5 T cell epitope-rich HIV regions of Gag, Pol, and Nef (G/P/N) directly fused to αCD40 (Flamar et. al., AIDS, 2013) or αDCIR mAbs. In vitro, these vaccines expand multi-functional and polyepitopic specific CD4+ and CD8+ T cells.
Methods: NHP were primed twice at weeks (W) 0 and 8 with MVA encoding G/P/N sequences encompassing the HIV5pep sequences and boosted with either αCD40.HIV5pep (n=6) or αDCIR.HIV5pep (n=6) (three ID injections of 250μg with 1 mg Poly-ICLC (Hiltonol) at W 12, 16 and 24). Two other groups of NHP received anti-DC vaccines at W 0, 4 and 12 (n=6 per group) followed by one MVA boost at W 22. Antibody and HIV5pep-specific T cell responses were detected by ELISA and IFNγ-ELISPOT performed two weeks after each immunization.
Results: IgG titers were weak (<200) or undetectable following the two MVA primes but were observed in all animals following the DC-targeting vaccinations (∼5,000 1/EC50). Two weeks after each of DC-targeting vaccine boosts, HIV5pep-specific T cells were boosted to median 150, 503 and 388 SFC/106 PBMC for αDCIR.HIV5pep and 350, 1055 and 533 for αCD40.HIV5pep compared to after the second MVA vaccination [145 and 98 for these two groups]. Globally, DC vaccines boosted significantly T cell responses as compared to baseline (+648 SFC/106 PBMC, P<.0005). In non-MVA primed groups, median HIV5pep-specific T cells responses following each DC-targeting vaccine were respectively 43, 135, 148 SFC/106 PBMC for αDCIR.HIV5pep and 118, 190, 198 SFC/106 PBMC for αCD40.HIV5pep. Those responses increased to 200 and 310 SFC/106 PBMC two weeks after MVA boost.
Conclusions: These DC-targeting vaccines elicited broad HIV peptide-specific T cell responses in both priming and boost settings. These data support their potential for further development, in particular as a component of a therapeutic vaccination strategy.
