(396e) Silk Microneedle Skin Patches for Tunable HIV Subunit Vaccine Delivery

Development of a prophylactic HIV vaccine requires novel immunogen design and vaccine delivery strategies. Recent studies in our laboratories have shown that the kinetics of vaccine release modulate humoral immune responses. To control kinetics of prophylactic HIV vaccine, we developed a submicron-scale dissolving microneedle patch (MN) with release kinetics dependent on MN composition. We utilized silk protein to encapsulate an HIV envelope trimer (BG505 SOSIP) immunogen and adjuvants with poly(acrylic acid) (PAA) base. Upon dermal application, rapid dissolution of PAA is followed by silk beta sheet-dependent sustained release of encapsulated vaccine. In mice, whole animal imaging showed higher model antigen retention over one week in the skin with minimal local inflammation for silk MNs compared to equivalent intradermal injections. Antigenicity of SOSIP was maintained in silk as determined by binding to broadly neutralizing antibodies (bNAbs: PGT151, PGT145, PGT121, VRCO1) without binding to non-bNAb 14e. In mice, vaccine delivery in silk MNs promoted and sustained germinal center (GC) responses in lymph nodes with significantly higher GC B cells, plasmablasts and T follicular helper (Tfh) cells for upto 14 days following immunization compared to intradermal injections. Significant increases in MN induced anti-SOSIP IgG titers post boost correlated with Tfh induced increase in plasma CXCL13, a biomarker for strong antibody responses. Taken together, these results indicate the potential of silk microneedles for tunable HIV subunit vaccine delivery.