Microneedle array patch delivery of Shigella flexneri 2a GMMA

Abstract

Shigella infections have long been a significant contributor to global diarrheal mortality, yet no approved Shigella vaccines are currently available. Generalized Modules for Membrane Antigens (GMMA) has emerged as an innovative platform for developing vaccines against Shigella. Here, for the first time, this technology was combined with a microneedle array patch (MAP), a transdermal vaccine delivery system, as an attractive method to overcome the drawbacks of parenteral administration routes. First, we demonstrated that two types of MAPs, the coated (C-MAP) and powder-attached (P-MAP) formats, loaded with Shigella flexneri 2a GMMA maintained their quality throughout the manufacturing process and was stable during storage for one month. Next, we evaluated the immunogenicity induced by the two GMMA MAP vaccines in mice. Both C-MAP and P-MAP elicited anti-OAg serum IgG and bactericidal antibodies comparable to those obtained via intramuscular (IM) injection of 5 mu g/ dose of OAg. Furthermore, P-MAP elicited the strongest long-term immunogenicity. Ultimately, P-MAP delivery of S. flexneri 2a GMMA induced the most robust and durable immune response, suggesting the possibility of combining these two platforms for Shigella vaccine development.