Spatial Segregation Within Dissolving Microneedle Patches Overcomes Antigenic Interference and Enables Potent Bivalent Influenza–RSV Vaccination in Mice

作者：Feng Fan, Yehong Wu, Hongzhe Lin, Xin Zhang, Limei Wang, He Yue, Shijie Zhang, M Y Zhang, Gan Zhao, Rong Xiang, Yating Kang, Mingyue Chen, Zhuang Li, Yibing Guo, Hang Zhou, Chen Zhao, Man-Chuan Wang, Jian-Yang Gu, Bin Wang, Xiao‐Ming Gao · 发表于：Vaccines · 年份：2025 · DOI：10.3390/vaccines13121213 · 被引用次数：2 · 研究领域：Advancements in Transdermal Drug Delivery、Advanced Drug Delivery Systems、Inhalation and Respiratory Drug Delivery

Background/Objectives: Given the overlapping seasonality of influenza (Flu) and respiratory syncytial virus (RSV) infections in human populations, Flu–RSV combination vaccines are urgently needed. However, development of combo-vaccines is often faced with intra-vaccine interference which could compromise vaccination outcomes. Here we present an approach to overcoming this problem using a microneedle array patch (MAP)-based combo-vaccine with minimum intra-vaccine interference. Methods: Vaccine-laden dissolving MAPs were fabricated using a two-step micro-molding process with polyvinyl alcohol as major excipient. A partition-loading strategy was adopted to ensure spatially segregated distribution of a split-virus Flu vaccine and recombinant prefusion protein of RSV in separate MAP sectors. Serum samples from BALB/c mice post-vaccination were assessed for titers of binding and neutralizing antibodies against the viruses. Live virus challenge studies were carried out to assess the protection efficacy of the MAP-based vaccines. Results: Although i.m. administered standalone Flu and RSV vaccines were able to induce strong IgG responses in BALB/c mice, bidirectional intra-vaccine interference was observed when the two vaccines were co-administered in premixed form. However, when the two vaccines were loaded onto nonoverlapping sectors of D-MAPs for intradermal vaccination, the intra-vaccine interference effect was effectively overcome. The partition-loaded MAP-Flu/RSV combo-vaccine ...