Immunization with synthetic LbL microparticle vaccine administered using a microneedle patch elicits humoral and cellular immune responses and protects mice from challenge with respiratory syncytial virus

Synthetic vaccines made by layer-by-layer fabrication of microparticles (LbL-MP represent a novel method of delivering peptide antigens to elicit protective immune responses in the absence of complex adjuvant and without concomitant inflammation. We incorporated LbL-MP into a microneedle patch that delivers the vaccine directly to the immunologically rich environment of the skin in a minimally-invasive manner. BALB/c mice immunized with microneedle patches loaded with LbL-MP bearing two conserved epitopes of respiratory syncytial virus (RSV) generated humoral and cellular immune responses and were protected from virus challenge. The vaccine contained a conserved CX3C chemokine mimic epitope from the RSV attachment (G) protein that contributes to Th2-skewed inflammatory responses. Patch-immunized mice developed RSV-G-specific antibody titers comparable to the titers induced by direct injection of the vaccine into the footpad. The mice developed T-cell responses, including effector CTL, against a CD8 epitope of the RSV-M2 protein included in the vaccine. While footpad injection elicited both Th2 (IL-5) and Th1 (IFNγ) responses, microneedle patch immunization elicited a dominant Th1 response with very low Th2 response. A similar pattern of Th1u003eTh2 was seen in C57BL/6 mice immunized with a patch loaded with LbL-MP containing epitopes of the P. falciparum circumsporozoite protein, suggesting that the Th1 dominance was not antigen- or strain-specific, but rather an outcome of LbL-MP microneedle patch immunization. These studies demonstrate that LbL-MP retain their integrity and potency when delivered via microneedle patch, and favor Th1 immune responses that may be more effective against acute infection.