The immune system of astronauts might become weakened in the microgravity environment in space, and the dormant varicella-zoster virus (VZV) in the body might be reactivated, seriously affecting their work and safety. For working in orbit for the long term, there is currently no efficient and durable delivery system of general vaccines in a microgravity environment. Accordingly, based on the previous foundation, we designed, modified, and synthesized a biodegradable and biocompatible copolymer, polyethylene glycol-polysulfamethazine carbonate urethane (PEG-PSCU) that could be mainly adopted to fabricate a novel sustained-release microneedle (S-R MN) patch. Compared with conventional biodegradable microneedles, this S-R MN patch could not only efficiently encapsulate protein vaccines (varicella-zoster virus glycoprotein E, VZV gE) but also further prolong the release time of VZV gE in a simulated microgravity (SMG) environment. Eventually, we verified the activation of dendritic cells by VZV gE released from the S-R MN patch in an SMG environment and the positive bioeffect of activated dendritic cells on lymphocytes using an in vitro lymph node model. This study is of great significance for the exploration of long-term specific immune responses to the VZV in an SMG environment.